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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 1,207 records · Page 67
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Beyond the effectiveness factor: Multi-step reactions with intraparticle diffusion limitations

Though common in many industrial chemical processes, multi-step reactions occurring within porous catalyst particles provide significant challenges to previously established modeling frameworks. In this work, a system of reaction-diffusion equations is solved analytically via eigenanalysis. The intraparticle concentration profiles are integrated over the particle volume to obtain effectiveness factors for each reacting species, referred to herein as a multi-step effectiveness vector (MEV). The MEV solution is tested for the case of uniform flow past a stationary catalyst particle with a state-of-the-art, multi-step reaction scheme for fluid catalytic cracking (FCC). Outputs from particle-resolved direct numerical simulation (DNS) are compared to outputs from ordinary differentials with effective reaction closures coming from the MEV solution, the classic single-step effectiveness factor (SEF) (R. Aris, 'The mathematical theory of diffusion and reaction in permeable catalysts: The theory of the steady state,' Oxford University Press, 1975), and utilizing the intrinsic rates as-is. When compared to DNS, the MEV solution shows excellent agreement for the formation of all species and quantitatively captures the intraparticle concentration profiles. By contrast, the intrinsic treatment shows an over-prediction for product formation and the SEF treatment shows mixed levels of accuracy that depend upon the reaction coupling. Specifically, the SEF treatment accurately characterizes product formation if the kinetic scheme is weakly coupled but shows significant departure if stronger coupling is present. The computational cost associated with the MEV solution is associated with eigendecomposition of the Thiele matrix, an N x N matrix where N is the number of reacting components. Overall, the method is shown to be relatively easy to implement and may significantly enhance the fidelity of chemical reactor simulations that employ multi-step reaction schemes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2016

A window into occupant-driven energy outcomes: Leveraging sub-metering infrastructure to examine psychosocial factors driving long-term outcomes of short-term competition-based energy interventions

Competition-based “energy saving” interventions are increasingly promoted as an effective strategy for reducing energy consumption in buildings with large occupant controlled electrical loads. However, the factors that drive energy savings in such interventions are not well understood, nor are the impacts of short-term competitions on long-term energy performance. A total of 39 8-occupant suites in a freshman residence hall were instrumented with “smart” electric meters, which recorded circuit-level electricity consumption at 15-minute intervals. During a three-week Fall 2014 competition, suites competed to reduce their overall electricity demand and achieved a 6.4% reduction in whole-building demand overall and a 12% reduction during hours of peak demand (from 12:00 to 19:00), despite peak seasonal temperatures and all-time record electricity demand. Analysis incorporating weather-normalized HVAC demand after the competition showed a significant “rebound” for a large portion of the suites (19), however 12 suites made further reductions, and the remainder maintained demand at the competition level. As a result, we compared energy data with self-reported survey data and identified self-efficacy beliefs, pro-environmental behaviors, and sense of affiliation with other residents of the hall as key factors distinguishing the suites with the greatest and most persistent reductions in demand from suites that maintained or increased demand.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2025

Impact of grassland fire dynamics on particulate emission factors

Understanding particulate emission factors in grassland fires is critical for improving air quality assessments and refining emissions inventories. This study explores the dynamic and heterogeneous nature of fire processes and their influence on particulate emissions. Traditional emission factor inventories often rely on static values, overlooking the spatially and temporally variable dynamics of fire behavior. Through field experiments conducted at Konza Prairie Biological Station measuring emissions with uncrewed aerial vehicles, and computational modeling using HIGRAD/FIRETEC, this research highlights the dependency of emission production on localized fire dynamics, including ignition patterns, fuel properties, and atmospheric conditions. The results demonstrate a need for fire dynamic considerations to accurately capture emissions variability.

09 BIOMASS FUELS↗
DOE OSTI2023

Structural basis of DNA binding by the WhiB-like transcription factor WhiB3 in Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) WhiB3 is an iron–sulfur cluster-containing transcription factor belonging to a subclass of the WhiB-Like (Wbl) family that is widely distributed in the phylum Actinobacteria. WhiB3 plays a crucial role in the survival and pathogenesis of Mtb. It binds to the conserved region 4 of the principal sigma factor (σ A 4 ) in the RNA polymerase holoenzyme to regulate gene expression like other known Wbl proteins in Mtb. However, the structural basis of how WhiB3 coordinates with σ A 4 to bind DNA and regulate transcription is unclear. Here we determined crystal structures of the WhiB3:σ A 4 complex without and with DNA at 1.5 Å and 2.45 Å, respectively, to elucidate how WhiB3 interacts with DNA to regulate gene expression. These structures reveal that the WhiB3:σ A 4 complex shares a molecular interface similar to other structurally characterized Wbl proteins and also possesses a subclass-specific Arg-rich DNA-binding motif. We demonstrate that this newly defined Arg-rich motif is required for WhiB3 binding to DNA in vitro and transcriptional regulation in Mycobacterium smegmatis. Together, our study provides empirical evidence of how WhiB3 regulates gene expression in Mtb by partnering with σ A 4 and engaging with DNA via the subclass-specific structural motif, distinct from the modes of DNA interaction by WhiB1 and WhiB7.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Pair creation energy and Fano factor of silicon measured at 185 K using 55 F e X-rays

Here, the pair creation energy, ωω and the Fano factor of silicon were measured using a CCD sensor and X-rays from an 55 Fe source. The measurements were performed at a sensor temperature of 185K. The pair creation energy was measured for X-rays in the 1.7–6.5 keV range. The measured pair creation energy is ω=(3.650 ± 0.009) eV at the MnK α line energy. The Fano factor at this energy is F = 0.128±0.001. The agreement with theory and previous measurements is satisfactory. The system gain was obtained from flat field exposures using the Poisson distribution properties. These results and the details of our measurement procedure are presented below.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2025

High fidelity multiphysics tightly coupled model for a lead cooled fast reactor concept and application to statistical calculation of hot channel factors

A tightly coupled multiphysics code system is established using the MOOSE framework for hot channel factor (HCF) evaluation on a Lead Fast Reactor (LFR) concept. The coupled system is driven by the Griffin multiphysics coupling capability under which the MOOSE Heat Transfer module and NekRS computational fluid dynamics solver are coupled for conjugate heat transfer using the Cardinal application. The coupled capability is demonstrated on an LFR assembly model based on materials and geometry of a prototypical lead-cooled fast reactor design by Westinghouse Electric Company, LLC. Moreover, the work integrates the Multiphysics Object Oriented Simulation Environment (MOOSE) Stochastic Tools Module (STM) to perform calculations for statistical analysis of HCF. Furthermore, the coupling strategy and workflow demonstrated in this paper is not only useful for predicting accurate hot channel factors for different kinds of advanced reactors but also for other engineering applications such as control rod worth assessment, generation of high-fidelity database for Artificial intelligence (AI)/machine learning (ML) training, design optimization and multi-resolution modeling.

Cardinal↗
DOE OSTI2020

QCD factorization and universality of jet cross sections in heavy-ion collisions

In this work, we review a recently proposed phenomenological framework to establish the notions of QCD factorization and universality of jet cross sections in the heavy-ion environment. First results of a global analysis of the nuclear modification factor of inclusive jets are presented where we extract medium modified jet functions using a Monte Carlo sampling approach. We observe that gluon jets are significantly more suppressed than quark jets. In addition, we study the jet radius dependence of the inclusive jet cross section in heavy-ion collisions and comment on a recent measurement from CMS. By considering for example jet substructure observables it will be possible to test the universality of the extracted medium jet functions. We thus expect that the presented results will eventually allow for extractions of medium properties with a reduced model bias.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2020

Theoretical power-law relationship between permeability and formation factor

Permeability k and formation factor F are important petrophysical properties that have broad applications to reservoir engineering. Although well-log analysis has advanced reservoir characterizations, direct measurement of k is still not available. Accordingly, resistivity logs and more particularly formation factor have been frequently used to estimate k. In this study, we present a theoretical framework to relate k to F. We use power-law scaling from continuum percolation theory to develop a theoretic relationship between k and F, which is similar in form to a published power-law equation with empirical coefficients. Our result gives a physical interpretation to this empirical relationship. We also compare power-law scaling laws from percolation theory with data derived from experimental measurements and numerical simulations in the literature. Finally, using the Curve Fitting toolbox of MATLAB, the parameters of the power-law equations are determined, and the significance of the non-universal power laws are discussed.

42 ENGINEERING↗
DOE OSTI2021

Measurement of proton electromagnetic form factors in the time-like region using initial state radiation at BESIII

The electromagnetic process e + e - → $p\bar{p}$ is studied with the initial-state-radiation technique using 7.5 fb -1 of data collected by the BESIII experiment at seven energy points from 3.773 to 4.600 GeV. The Born cross section and the effective form factor of the proton are measured from the production threshold to 3.0 GeV/c 2 using the $p\bar{p}$ invariant-mass spectrum. The ratio of electric and magnetic form factors of the proton is determined from the analysis of the proton-helicity angular distribution.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2022

Nucleon form factors and parton distributions in nonlocal chiral effective theory

In this work, we present a review of recent applications of nonlocal chiral effective theory to hadron structure studies. Starting from a nonlocal meson-baryon effective chiral Lagrangian, we show how the introduction of a correlation function representing the finite extent of hadrons regularizes the meson loop integrals and introduces momentum dependence in vertex form factors in a gauge invariant manner. We apply the framework to the calculation of nucleon electromagnetic form factors, unpolarized and polarized parton distributions, as well as transverse momentum dependent distributions and generalized parton distributions. Assuming that the nonlocal behavior is a general property of all interactions, we also discuss the application to the lepton anomalous magnetic moment in nonlocal QED.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2016

The role of hepatocyte nuclear factor 4-alpha in perfluorooctanoic acid- and perfluorooctanesulfonic acid-induced hepatocellular dysfunction

Perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), chemicals present in a multitude of consumer products, are persistent organic pollutants. Both compounds induce hepatotoxic effects in rodents, including steatosis, hepatomegaly and liver cancer. The mechanisms of PFOA- and PFOS-induced hepatic dysfunction are not completely understood. We present evidence that PFOA and PFOS induce their hepatic effects via targeting hepatocyte nuclear factor 4-alpha (HNF4α). Human hepatocytes treated with PFOA and PFOS at a concentration relevant to occupational exposure caused a decrease in HNF4α protein without affecting HNF4α mRNA or causing cell death. RNA sequencing analysis combined with Ingenuity Pathway Analysis of global gene expression changes in human hepatocytes treated with PFOA or PFOS indicated alterations in the expression of genes involved in lipid metabolism and tumorigenesis, several of which are regulated by HNF4α. Further investigation of specific HNF4α target gene expression revealed that PFOA and PFOS could promote cellular dedifferentiation and increase cell proliferation by down regulating positive targets (differentiation genes such as CYP7A1) and inducing negative targets of HNF4α (pro-mitogenic genes such as CCND1). Furthermore, in silico docking simulations indicated that PFOA and PFOS could directly interact with HNF4α in a similar manner to endogenous fatty acids. Collectively, these results highlight HNF4α degradation as novel mechanism of PFOA and PFOS-mediated steatosis and tumorigenesis in human livers. - Highlights: • PFOA and PFOS cause decreased HNF4α protein expression in human hepatocytes. • PFOA and PFOS promote changes associated with lipid metabolism and carcinogenesis. • PFOA and PFOS induced changes in gene expression associated with cellular dedifferentiation. • PFOA and PFOS induce expression of Nanog, a transcription factor involved in stem cell development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4{sup +/+} wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4{sup +/−} heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca{sup ++} homeostasis. ATO induces Ca{sup ++}-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca{sup ++} homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4{sup +/−} mice. • Changes in macrophage functions can be attenuated by Ca{sup ++} homeostasis regulators.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in the future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was accomplished after cell treatment. • TAT-CNTF can be efficiently loaded on oxidized PVA cylinders for local delivery. • TAT-CNTF features make it ideal for peripheral nerve regeneration therapies.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Epidermal growth factor receptor signaling mediates aldosterone-induced profibrotic responses in kidney

Aldosterone has been recognized as a risk factor for the development of chronic kidney disease (CKD). Studies have indicated that enhanced activation of epidermal growth factor receptor (EGFR) is associated with the development and progression of renal fibrosis. But if EGFR is involved in aldosterone-induced renal fibrosis is less investigated. In the present study, we examined the effect of erlotinib, an inhibitor of EGFR tyrosine kinase activity, on the progression of aldosterone-induced renal profibrotic responses in a murine model underwent uninephrectomy. Erlotinib-treated rats exhibited relieved structural lesion comparing with rats treated with aldosterone alone, as characterized by glomerular hypertrophy, mesangial cell proliferation and expansion. Also, erlotinib inhibited the expression of TGF-β, α-SMA and mesangial matrix proteins such as collagen Ⅳ and fibronectin. In cultured mesangial cells, inhibition of EGFR also abrogated aldosterone-induced expression of extracellular matrix proteins, cell proliferation and migration. We also demonstrated that aldosterone induced the phosphorylation of EGFR through generation of ROS. And the activation of EGFR resulted in the phosphorylation of ERK1/2, leading to the activation of profibrotic pathways. Taken together, we concluded that aldosterone-mediated tissue fibrosis relies on ROS induced EGFR/ERK activation, highlighting EGFR as a potential therapeutic target for modulating renal fibrosis. - Highlights: • EGFR was involved in aldosterone-induced renal profibrotic responses. • Aldosterone-induced EGFR activation was mediated by MR-dependent ROS generation. • EGFR activated the MAPK/ERK1/2 signaling to promote renal fibrosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Nuclear respiratory factor-1 and bioenergetics in tamoxifen-resistant breast cancer cells

Acquired tamoxifen (TAM) resistance is a significant clinical problem in treating patients with estrogen receptor α (ERα)+ breast cancer. We reported that ERα increases nuclear respiratory factor-1 (NRF-1), which regulates nuclear-encoded mitochondrial gene transcription, in MCF-7 breast cancer cells and NRF-1 knockdown stimulates apoptosis. Whether NRF-1 and target gene expression is altered in endocrine resistant breast cancer cells is unknown. We measured NRF-1and metabolic features in a cell model of progressive TAM-resistance. NRF-1 and its target mitochondrial transcription factor A (TFAM) were higher in TAM-resistant LCC2 and LCC9 cells than TAM-sensitive MCF-7 cells. Using extracellular flux assays we observed that LCC1, LCC2, and LCC9 cells showed similar oxygen consumption rate (OCR), but lower mitochondrial reserve capacity which was correlated with lower Succinate Dehydrogenase Complex, Subunit B in LCC1 and LCC2 cells. Complex III activity was lower in LCC9 than MCF-7 cells. LCC1, LCC2, and LCC9 cells had higher basal extracellular acidification (ECAR), indicating higher aerobic glycolysis, relative to MCF-7 cells. Mitochondrial bioenergetic responses to estradiol and 4-hydroxytamoxifen were reduced in the endocrine-resistant cells compared to MCF-7 cells. These results suggest the acquisition of altered metabolic phenotypes in response to long term antiestrogen treatment may increase vulnerability to metabolic stress. - Highlights: • NRF-1 and TFAM expression are higher in endocrine-resistant breast cancer cells. • Oxygen consumption rate is similar in endocrine-sensitive and resistant cells. • Mitochondrial reserve capacity is lower in endocrine-resistant cells. • Endocrine-resistant breast cancer cells have increased glycolysis. • Bioenergetic responses to E2 and tamoxifen are lower in endocrine-resistant cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Mechano-growth factor protects against mechanical overload induced damage and promotes migration of growth plate chondrocytes through RhoA/YAP pathway

Highlights: • Cyclic mechanical stress induces MGF expression and MGF protects against mechanical overload induced apoptosis and inflammation. • MGF regulates YAP activation to induce chondrocytes migration via RhoA. • MGF promotes focal adhesion formation via RhoA-YAP pathway. Epiphyseal growth plate is highly dynamic tissue which is controlled by a variety of endocrine, paracrine hormones, and by complex local signaling loops and mechanical loading. Mechano growth factor (MGF), the splice variant of the IGF-I gene, has been discovered to play important roles in tissue growth and repair. However, the effect of MGF on the growth plate remains unclear. In the present study, we found that MGF mRNA expression of growth plate chondrocytes was upregulated in response to mechanical stimuli. Treatment of MGF had no effect on growth plate chondrocytes proliferation and differentiation. But it could inhibit growth plate chondrocytes apoptosis and inflammation under mechanical overload. Moreover, both wound healing and transwell assay indicated that MGF could significantly enhance growth plate chondrocytes migration which was accompanied with YAP activation and nucleus translocation. Knockdown of YAP with YAP siRNA suppressed migration induced by MGF, indicating the essential role of YAP in MGF promoting growth plate chondrocytes migration. Furthermore, MGF promoted YAP activation through RhoA GTPase mediated cytoskeleton reorganization, RhoA inhibition using C3 toxin abrogated MGF induced YAP activation. Importantly, we found that MGF promoted focal adhesion(FA) formation and knockdown of YAP with YAP siRNA partially suppressed the activation of FA kinase, implying that YAP is associated with FA formation. In conclusion, MGF is an autocrine growth factor which is regulated by mechanical stimuli. MGF could not only protect growth plate chondrocytes against damage by mechanical overload, but also promote migration through activation of RhoA/YAP signaling axis. Most importantly, our findings indicate that MGF promote cell migration through YAP mediated FA formation to determine the FA-cytoskeleton remodeling.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Hepatitis B virus suppresses the secretion of insulin-like growth factor binding protein 1 to facilitate anti-apoptotic IGF-1 effects in HepG2 cells

Highlights: • HBV replication alters host cell gene expression in HepG2 cells. • HBV replication downregulates IGFBP1 expression and secretion. • HBx expression alone is sufficient to modulate IGFBP1 expression. • Knockdown of IGFBP1 reduces thapsigargin- and staurosporine-induced apoptosis. • IGFBP1 inhibits the anti-apoptotic effects of IGF-1. Hepatitis B virus (HBV) infection is a major global health burden as chronic hepatitis B (CHB) is associated with the development of liver diseases including hepatocellular carcinoma (HCC). To gain insight into the mechanisms causing HBV-related HCC, we investigated the effects of HBV replication on global host cell gene expression using human HepG2 liver cells. By microarray analysis, we identified 54 differentially expressed genes in HBV-replicating HepG2 cells. One of the differentially-expressed genes was insulin-like growth factor binding protein 1 (IGFBP1) which was downregulated in HBV-replicating cells. Consistent with the gene expression data, IGFBP1 was suppressed at both the cellular and secreted protein levels in the presence of HBV replication. Transient transfection experiments with an inducible plasmid encoding the HBV X protein (HBx) revealed that HBx alone was sufficient to modulate IGFBP1 expression. Small interference RNA (siRNA)-mediated loss of function studies revealed that knockdown of IGFBP1 reduced apoptosis induced by either thapsigargin (TG) or staurosporine (STS). Treatment of cells with recombinant insulin-like growth factor 1 (IGF-1) decreased both TG- or STS-induced apoptosis. Interestingly, addition of recombinant IGFBP1 reversed the anti-apoptotic effect of IGF-1 on TG-induced, but not STS-induced, apoptosis. In conclusion, our results suggest an anti-apoptotic autocrine function of HBV-mediated downregulation of IGFBP1 in HepG2 cells. Such an effect may contribute to the development of HBV-mediated HCC by increasing pro-survival and anti-apoptotic IGF-1 effects.

60 APPLIED LIFE SCIENCES↗