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Results for “PROLIFERATION”

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 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

CHIQUITA1 maintains the temporal transition between proliferation and differentiation in Arabidopsis thaliana

ABSTRACT Body size varies widely among species, populations and individuals, depending on the environment. Transitioning between proliferation and differentiation is a crucial determinant of final organ size, but how the timing of this transition is established and maintained remains unknown. Using cell proliferation markers and genetic analysis, we show that CHIQUITA1 (CHIQ1) is required to maintain the timing of the transition from proliferation to differentiation in Arabidopsis thaliana. Combining kinematic and cell lineage-tracking studies, we found that the number of actively dividing cells in chiquita1-1 plants decreases prematurely compared with wild-type plants, suggesting CHIQ1 maintains the proliferative capacity in dividing cells and ensures that cells divide a specific number of times. CHIQ1 belongs to a plant-specific gene family of unknown molecular function and genetically interacts with three close members of its family to control the timing of proliferation exit. Our work reveals the interdependency between cellular and organ-level processes underlying final organ size determination.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Financial incentives for reducing proliferation risks

This article submitted for publication to the Bulletin of Atomic Scientists explains the possible financial incentives for financial institutions and large integrators to reduce nuclear proliferation risks by including anti-proliferation measures in their due diligence and requiring their suppliers to meet heightened compliance standards. Because manufacturers of dual-use nuclear goods are diverse and numerous outreach is difficult. However, financial institutions and large integrators work with nearly all dual-use manufacturers, making financial institutions and integrators well-positioned to increase awareness of proliferation and trafficking risks throughout the nuclear supply chain

anti-proliferation↗
DOE OSTI2021

HPRT promotes proliferation and metastasis in head and neck squamous cell carcinoma through direct interaction with STAT3

Highlights: • The higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. • Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers. • HPRT directly interacted with STAT3. • Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect against HNSCC xenografts. Increasing effort has been put into finding novel molecular pathways to improve the efficiency of EGFR inhibitors against head and neck squamous cell cancer (HNSCC). In this study, we performed data mining and bioinformatically analysed RNA-Seq data downloaded from TCGA and confirmed that higher expression of HPRT in HNSCC tissue was related to poor prognosis of patients. Then, we conducted in vitro and in vivo loss- and gain-of-function experiments to demonstrate the role of HPRT in HNSCC cell lines. Overexpression of HPRT increased the gene expression of epithelial mesenchymal transition markers via direct interaction with STAT3. Knocking down HPRT significantly decreased tumour growth and enhanced the anticancer effect of EGFR inhibitors against HNSCC xenografts. In conclusion, HPRT is a binding partner of STAT3 that promotes EMT and proliferation. Our findings support HPRT as a promising prognostic indicator and potential therapeutic target for HNSCC.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Period proliferation in periodic states in cyclically sheared jammed solids

Athermal disordered systems can display a remarkable response to an applied oscillatory shear: After a relatively few shearing cycles, the system falls into a configuration that had already been visited in a previous cycle. After this point the system repeats its dynamics periodically despite undergoing many particle rearrangements during each cycle. We study here the behavior of orbits as we approach the jamming point in simulations of jammed particles subject to oscillatory shear at fixed pressure and zero temperature. As the pressure is lowered, we find that it becomes more common for the system to find periodic states where it takes multiple cycles before returning to a previously visited state. Thus, there is a proliferation of longer periods as the jamming point is approached.

36 MATERIALS SCIENCE↗
DOE OSTI2017

Proliferation of mouse endometrial stromal cells in culture is highly sensitive to lysophosphatidic acid signaling

Endometrial stromal cells (ESCs) proliferate rapidly both in vivo and in vitro. Here we show that proliferation of ESCs in vitro is strongly dependent on lysophosphatidic acid (LPA) signaling. LPA is produced by autotaxin (ATX) and induces various kinds of cellular processes including migration, proliferation and inhibition of cell death possibly through six G protein-coupled receptors (LPA{sub 1-6}). We found that ESCs proliferated rapidly in vitro in an autocrine manner and that the proliferation was prominently suppressed by either an ATX inhibitor (ONO-8430506) or an LPA{sub 1/3} antagonist (Ki16425). Among the cells lines tested, mouse ESCs were the most sensitive to these inhibitors. Proliferation of ESCs isolated from either LPA{sub 1}- or LPA{sub 3}-deficient mice was comparable to proliferation of ESCs isolated from control mice. An LPA receptor antagonist (AM095), which was revealed to be a dual LPA{sub 1}/LPA{sub 3} antagonist, also suppressed the proliferation of ESCs. The present results show that LPA signaling has a critical role in the proliferation of ESCs, and that this role is possibly mediated redundantly by LPA{sub 1} and LPA{sub 3}. - Highlights: • Uterine endometrial stromal cells (ESCs) proliferate rapidly both in vivo and in vitro. • ESCs proliferated in vitro in an autocrine fashion. • Proliferation of mouse ESCs was prominently suppressed by inhibitors of lysophosphatidic acid (LPA) signaling. • LPA receptors, LPA{sub 1} and LPA{sub 3}, had redundant role in supporting the proliferation of ESCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

LncRNA-MALAT1 promotes CPC proliferation and migration in hypoxia by up-regulation of JMJD6 via sponging miR-125

Highlights: • MALAT1 was up-regulated in CPCs in hypoxia conditions. • MALAT1 suppression inhibited CPCs proliferation and migration after hypoxia-inducing stimuli. • MALAT1 modulated CPCs proliferation and migration through MALAT1/miR-125/JMJD6 axis under hypoxia conditions. The death of cardiomyocytes after myocardial infarction (MI) often leads to ventricular remodeling as well as heart failure (HF). The cardiac progenitor cells (CPCs) have the ability to regenerate functional heart muscle in patients after MI, which provides a promising method for MI-induced HF therapy. However, to date, CPCs can easily lose their proliferation ability in the infarcted myocardium. Therefore, exploring the mechanism for CPC proliferation is essential for CPC-based therapy in MI-induced HF. A previous study indicated that a hypoxic environment is essential for CPC proliferation, but the mechanism is not yet clear. In this work, we discovered that CoCl{sub 2}-induced hypoxia can promote CPC proliferation and migration. Additionally, long non-coding RNA MALAT1 expression was significantly up-regulated in the CoCl{sub 2}-induced hypoxia CPC model. MALAT1 suppression inhibited CPC proliferation and migration under hypoxic conditions. In addition, MALAT1 acted as a sponge for miR-125. The miR-125 inhibitor restored the proliferation and migration potentials of CPCs after a MALAT1 knockdown in hypoxia. A further study demonstrated that JMJD6 was a target of miR-125 whose expression was negatively regulated by miR-125. JMJD6 knockdown blocked miR-125 inhibitor's protective effect on CPC function in hypoxia. Ultimately, our finding demonstrated that MALAT1 can modulate CPC proliferation and migration potential through the miR-125/JMJD6 axis in hypoxia. Our finding provided a new regulatory mechanism for CPC proliferation in hypoxia, which provided a new target for MI-induced HF therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MicroRNA-374b promotes the proliferation and differentiation of neural stem cells through targeting Hes1

Highlights: • miR-374b expression was upregulated during NSC differentiation. • miR-374b promoted NSC proliferation and differentiation to neurons. • Hes1 was identified as a target gene of miR-374b. • miR-374b regulated NSC proliferation and differentiation by Hes1 Accumulating evidence has documented that microRNAs (miRNAs) are critical regulators of neural stem cell (NSC) proliferation and differentiation. MiRNA-374b (miR-374b) has been reported to play an important role in regulating various cellular processes, such as proliferation and differentiation. However, whether miR-374b is involved in NSC proliferation and differentiation remains unclear. In this study, we investigated the potential role of miR-374b in regulating NSC proliferation and differentiation to elucidate the underlying molecular mechanism. Our results showed that miR-374b expression was significantly upregulated during NSC differentiation. Functional experiments showed that overexpression of miR-374b promoted NSC proliferation and differentiation to neurons. By contrast, miR-374b inhibition showed the opposite effect. Hairy and enhancer of split 1 (Hes1), a master regulator of neurogenesis, was predicted as a potential target gene of miR-374b by bioinformatics analysis. Dual-luciferase reporter assays showed that miR-374b could directly target the 3′-untranslated region of Hes1. Further experiments showed that miR-374b negatively regulated the mRNA and protein expression of Hes1 in NSCs. Moreover, overexpression of Hes1 significantly reversed the miR-374b overexpression-mediated effect on NSC proliferation and differentiation. In addition, knockdown of Hes1 abrogated the miR-374b inhibition-mediated effect on NSC proliferation and differentiation. Taken together, these results demonstrate that miR-374b regulates the proliferation and differentiation of NSCs through targeting Hes1 and suggest that miR-374b is a potential target for modulating NSC-mediated neurogenesis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Serum extracellular vesicles promote proliferation of H9C2 cardiomyocytes by increasing miR-17-3p

Highlights: • Serum extracellular vesicles promotes H9C2 cardiomyocytes proliferation. • miR-17-3p mediates the pro-proliferation effects. • TIMP3 is a target gene of miR-17-3p. Emerging evidence showed that cardiac proliferation played a significant role in the cardiac rehabilitation and repair. Extracellular vesicles (EVs) are known to regulate multiple cell functions, whereas the role of EVs in cardiac proliferation still remains unclear. In this study, we found that serum EVs promoted cell proliferation in rat heart myoblastic H9C2 cells with significantly increased expression level of miR-17-3p. Inhibition of miR-17-3p could decrease H9C2 cells proliferation induced by serum EVs. Additionally, we found that TIMP3 was a target of miR-17-3p in H9C2 cells proliferation and the expression of TIMP3 was downregulated by serum EVs. Meanwhile, inhibition of TIMP3 increased cardiac proliferation. In conclusion, results of our study indicated that serum EVs could promote the proliferation of H9C2 cells via regulating miR-17-3p/TIMP3, which may be a potential therapeutic target for treatment of cardiac injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Roles of SDF-1/CXCR4 axis in cartilage endplate stem cells mediated promotion of nucleus pulposus cells proliferation

Highlights: • NPCs proliferation was promoted by co-cultured CESCs and CESCs-CM in vitro. • SDF-1 and CXCR4 were expressed in a complementary pattern in CESCs and NPCs. • CESCs promoted NPCs proliferation partially via SDF-1/CXCR4 axis. • SDF-1/CXCR4 axis mainly activated ERK1/2 pathway rather than Akt pathway in NPCs. • CESCs upregulated TIMP1 expression in NPCs in a SDF-1/CXCR4 axis independent manner. Stem cells transplantation has shown considerable promise in intervertebral disc repair and low-back pain release. Cartilage endplate stem cells (CESCs) also showed potential for nucleus pulposus (NP) regeneration in a rabbit disc degeneration model, the precise mechanism was unclear. Here we investigated the effects of CESCs on NP cells (NPCs) proliferation and the mechanism in vitro. CESCs and NPCs were isolated from surgical specimens of degenerative human lumbar disc. NPCs were co-cultured with CESCs at a 1:1 ratio or cultured in CESCs conditioned medium (CESCs-CM). NPCs proliferation was evaluated by Ki-67 staining, CCK-8 assay and cell cycle analysis. Gene expressions were detected by qRT-PCR and activation of Akt and ERK1/2 was detected by western blot. CXCR4 antagonist AMD3100 was used to block SDF-1/CXCR4 axis. ERK1/2 and Akt inhibitors were used to block Akt and ERK1/2 activation. Results showed that NPCs proliferation was promoted by direct-contact co-culturing with CESCs as well as culturing in CESCs-CM. SDF-1 expression level in CESCs was significantly higher than that in NPCs, while CXCR4 was the opposite. Promotion of NPCs proliferation mediated by CESCs-CM could be partially attenuated by AMD3100. CESCs-CM activated both Akt and ERK1/2 in NPCs, while rhSDF-1 scarcely activated Akt but obviously activated ERK1/2. Akt and ERK1/2 inhibitors could partially inhibited CESCs-CM mediated promotion of NPCs proliferation and showed cumulative effect, while ERK1/2 inhibitor and AMD3100 could significantly abrogate SDF-1 mediated promotion of NPCs proliferation. Our results suggested that CESCs might promote NPCs proliferation in a paracrine pathway, which was partially mediated by SDF-1/CXCR4 axis via ERK1/2 signaling transduction pathway.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

COP9 signalosome subunit 6 mediates PDGF -induced pulmonary arterial smooth muscle cells proliferation

Highlights: • CSN6 is up-regulated in PASMCs stimulated with PDGF. • Activated PDGFR/PI3K/Akt signaling pathway up-regulats CSN6 in PDGF-induced PASMCs. • CSN6 increases β-TrCP ubiquitinated degradation and thereby up-regulates Cdc25A. • Up-regulation of Cdc25A promotes PDGF-induced PASMCs proliferation. Up-regulation of mammalian COP9 signalosome subunit 6 (CSN6) and consequent reduction of SCF ubiquitin ligase substrate receptor β-transduction repeat-containing protein (β-TrCP) have been shown to be associated with cancer cells proliferation. However, it is unclear whether CSN6 and β-TrCP are also involved in PDGF-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation. This study aims to address this issue and further explore its potential mechanisms. Our results indicated that PDGF phosphorylated Akt, stimulated PASMCs proliferation; while inhibition of PDGF receptor (PDGFR) by imatinib prevented these effects. PDGF further up-regulated CSN6 protein expression, this was accompanied with β-TrCP reduction and increase of Cdc25A. Inhibition of PDGFR/PI3K/Akt signaling pathway reversed PDGF-induced such changes and cell proliferation. Prior transfection of CSN6 siRNA blocked PDGF-induced β-TrCP down-regulation, Cdc25A up-regulation and cell proliferation. Furthermore, pre-treatment of cells with MG-132 also abolished PDGF-induced β-TrCP reduction, Cdc25A elevation and cell proliferation. In addition, pre-depletion of Cdc25A by siRNA transfection suppressed PDGF-induced PASMCs proliferation. Taken together, our study indicates that up-regulation of CSN6 by PDGFR/PI3K/Akt signaling pathway decreases β-TrCP by increasing its ubiquitinated degradation, and thereby increases the expression of Cdc25A, which promotes PDGF-induced PASMCs proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Astrocytes regulate the expression of Sp1R3 on oligodendrocyte progenitor cells through Cx47 and promote their proliferation

Many degenerative diseases of the central nervous system are associated with demyelination. Oligodendrocyte progenitor cells (OPCs) are potential stem cells that can differentiate into various cell types, including oligodendrocytes (OLs). Promoting the proliferation and differentiation of OPCs into mature OLs that can myelinate axons is the key to stimulate remyelination. Here, we report that astrocytes (ASTs) increase the number of sphingosine-1-phosphate receptors 3 (S1pR3) on OPCs and promote OPCs proliferation through a direct contact via connexin 47 (Cx47). Our results demonstrate that ASTs can regulate the proliferation of OPCs through Cx47-mediated induction of S1pR3 expression on OPCs. Cx47/S1pR3 remarkably increases the number of OPCs and promotes cell transition from the G1 to the S phase. Furthermore, inhibiting either Cx47 or S1pR3 decreases OPC proliferation. In summary, ASTs regulate the expression of S1pR3 in OPCs via Cx47, which could be a valuable approach for promoting OPC proliferation. This strategy may therefore represent a potential treatment for neurological diseases caused by OLs death and demyelination. - Highlights: • Astrocytes through direct contact (connexin 47), can increase the number of OPCs surface proliferation receptors (S1pR3). • The increased number of OPCs on surface of proliferation receptors (S1pR3), promoted proliferation of OPCs. • Blocking S1pR3 could decrease the proliferation of OPCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

MicroRNA-2400 promotes bovine preadipocyte proliferation

MicroRNAs (miRNAs) play critical roles in the proliferation of bovine preadipocytes. miR-2400 is a novel and unique miRNA from bovines. In the present study, we separated and identified preadipocytes from bovine samples. miR-2400 overexpression increased the rate of preadipocyte proliferation, which was analyzed with a combination of EdU and flow cytometry. Simultaneously, functional genes related to proliferation (PCNA, CCND2, CCNB1) were also increased, which was detected by real-time PCR. Furthermore, luciferase reporter assays showed that miR-2400 bound directly to the 3'untranslated regions (3′UTRs) of PRDM11 mRNA. These data suggested that miR-2400 could promote preadipocyte proliferation by targeting PRDM11. - Highlights: • miRNAs are important in bovine preadipocyte proliferation. • miR-2400 is a novel miRNA from bovines. • miR-2400 overexpression increased preadipocyte proliferation. • Functional genes related to preadipocyte proliferation were upregulated. • Preadipocyte proliferation was promoted by targeting PRDM11.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Dixdc1 targets CyclinD1 and p21 via PI3K pathway activation to promote Schwann cell proliferation after sciatic nerve crush

Dixdc1 (DIX domain containing-1), the mammalian homolog of Ccd1 (Coiled-coil-Dishevelled-Axin1), is a protein containing a coiled-coil domain and a Dishevelled-Axin (DIX) domain. As a novel component of the Wnt pathway, Dixdc1 has been reported to be able to promote neural progenitor proliferation and neuronal differentiation via Wnt/β-catenin signaling. But there still remains something unknown about Dixdc1 distribution and functions in the lesion and regeneration of the peripheral nervous system (PNS), so we tried to investigate dynamic changes of Dixdc1 expression in a rat sciatic nerve crush (SNC) model in this study. First of all, we detected SNC-induced increased levels of Dixdc1 in Schwann cells and interestingly identified parallel expression of PCNA (proliferation cell nuclear antigen) with Dixdc1. Besides, we observed up-regulated Dixdc1 during the process of TNF-α-induced Schwann cell proliferation. Also, we discovered that Dixdc1 could promote G1-S phase transition accompanied with the up-regulation of CyclinD1 and down-regulation of p21. More importantly, enhanced effects of Dixdc1 on cell proliferation were confirmed to be associated with PI3K activation. Not only blocking of the PI3K but Dixdc1 knockdown led to significantly decreased ability for proliferation, as well as down-regulation of CyclinD1 and up-regulation of p21. In summary, these data demonstrated that Dixdc1 might participate in Schwann cell proliferation by targeting CyclinD1 and p21 at least partially through the PI3K/AKT activation. - Highlights: • The dynamic changes and location of Dixdc1 after sciatic nerve crush. • Dixdc1 was associated with Schwann cell proliferation. • Dixdc1 promoted Schwann cell proliferation partly via PI3K/AKT pathway.

36 MATERIALS SCIENCE↗
DOE OSTI2017

LXR agonists promote the proliferation of neural progenitor cells through MEK-ERK pathway

The liver X receptors (LXRs) are transcriptional regulators of lipid homeostasis and may be critical for neurodegeneration and neurogenesis in vivo. However, it remains largely unknown about the role of LXRs and its agonists in the in vitro proliferation of neural progenitor cells (NPCs). Here we revealed for the first time that LXRs were markedly expressed in mouse NPCs and were critical for the in vitro proliferation. LXR agonists GW3965 and LXR623 promoted the proliferation of wildtype NPCs, but not NPCs from LXR double-knockout mice. Mechanistically, phosphorylation of MEK1/2 and ERK1/2 in NPCs was enhanced upon LXR agonist treatment, while abrogation of MEK/ERK phosphorylation by the inhibitors PD98059 and U0126 impaired the proliferation of wildtype NPCs in the presence or absence of LXR agonists. Collectively, our findings suggest that LXR agonists GW3965 and LXR623 can stimulate the NPC proliferation in LXR- and MEK/ERK-dependent manner. - Highlights: • LXRs are expressed and functional in the mouse neural progenitor cells (NPCs). • LXRs are essential for the in vitro proliferation of mouse NPCs. • LXR agonists stimulate the proliferation of wildtype NPCs, but not LXRαβ−/− cells. • Phosphorylation of ERK/MEK was enhanced by LXR agonists in wildtype NPCs. • Inhibition of MEK/ERK phosphorylation impaired the proliferation of NPCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Exchange proteins directly activated by cAMP induce the proliferation of rat anterior pituitary GH3 cells via the activation of extracellular signal-regulated kinase

Cyclic adenosine 3′-5’-monophosphate (cAMP) plays a crucial role in regulating pituitary cell proliferation and hormone synthesis. Recent evidence suggests that exchange proteins directly activated by cAMP (Epacs) may mediate the effects of cAMP. Here we used rat anterior pituitary GH3 cells as the experiment model to demonstrate that forskolin increased the proliferation of GH3 cells and the phosphorylation of ERK1/2, and these effects were inhibited by PKA or Epac inhibitors. Epac activator 8-pCPT-2′-O-Me-cAMP increased GH3 cell proliferation and this was blocked by ESI-09, an Epac inhibitor. In contrast, forskolin-induced phosphorylation of CREB was unaffected by Epac inhibition. Notably, increased phosphorylation of ERK1/2 was correlated with increased cyclin D3 expression in GH3 cells. Furthermore, knockdown of Epac as well as B-Raf and MEK inhibitors blocked 8-pCPT-2′-O-Me-cAMP induced proliferation of GH3 cells and the phosphorylation of ERK1/2. In conclusion, our study suggests that Epac mediates cAMP induced pituitary cell proliferation via B-Raf and MAPK dependent mechanism. - Highlights: • PKA and Epac mediate cAMP induced GH3 cell proliferation. • Activation or knockdown of Epac stimulates or inhibits GH3 cell proliferation. • Epac induces the phosphorylation of ERK1/2 in GH3 cells via B-Raf. • B-Raf and MEK inhibitors block cAMP induced GH3 cell proliferation.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Ghrelin promotes human non-small cell lung cancer A549 cell proliferation through PI3K/Akt/mTOR/P70S6K and ERK signaling pathways

Highlights: • Ghrelin promotes A549 cells proliferation through binding to GHSR. • Ghrelin activates PI3K/Akt/mTOR/P70S6K and ERK signaling pathways. • PI3K/Akt/mTOR/P70S6K and ERK signaling mediates ghrelin-induced A549 cells proliferation. Ghrelin is a gastric acyl-peptide that plays an important role in cell proliferation. In the present study, we explored the role of ghrelin in A549 cell proliferation and the possible molecular mechanisms. We found that ghrelin promotes A549 cell proliferation, knockdown of the growth hormone secretagogue receptor (GHSR) attenuated A549 cell proliferation caused by ghrelin. Ghrelin induced the rapid phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, ERK, mammalian target of rapamycin (mTOR) and P70S6K. PI3K inhibitor (LY 294002), ERK inhibitor (PD98059) and mTOR inhibitor (Rapamycin) inhibited ghrelin-induced A549 cell proliferation. Moreover, GHSR siRNA inhibited phosphorylation of PI3K, Akt, ERK, mTOR and P70S6K induced by ghrelin. Akt and mTOR/P70S6K phosphorylation was inhibited by LY 294002 but not by PD98059. These results indicate that ghrelin promotes A549 cell proliferation via GHSR-dependent PI3K/Akt/mTOR/P70S6K and ERK signaling pathways.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation of caveolin-1. • RXM inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. • Our findings expand our knowledge of the role of RXM in airway remodelling.

60 APPLIED LIFE SCIENCES↗