eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
Current issue Archive Manuscripts accepted About the journal Special issues Editorial board Abstracting and indexing Subscription Contact Instructions for authors
SCImago Journal & Country Rank
5/2018
vol. 14
 
Share:
Share:
more
 
 
abstract:
Basic research

MicroRNA-590-5p represses proliferation of human fetal airway smooth muscle cells by targeting signal transducer and activator of transcription 3

Shan Shi, Lianhua Jin, Sai Zhang, Haibo Li, Bo Zhang, Meihua Sun

Arch Med Sci 2018; 14, 5: 1093–1101
Online publish date: 2018/03/21
View full text
Get citation
ENW
EndNote
BIB
JabRef, Mendeley
RIS
Papers, Reference Manager, RefWorks, Zotero
AMA
APA
Chicago
Harvard
MLA
Vancouver
 
Introduction
Pediatric asthma has remained a health threat to children in recent years. The abnormal proliferation of airway smooth muscle (ASM) cells contributes to airway remodeling during development of asthma. MicroRNAs (miRNAs) are critical regulators of ASM cell proliferation during airway remodeling. miR-590-5p has been reported to regulate cell proliferation in various cell types. However, it remains unclear whether miR-590-5p regulates ASM cell proliferation. In this study, we aimed to investigate the potential role of miR-590-5p in regulating fetal ASM cell proliferation in vitro stimulated by platelet-derived growth factor (PDGF).

Material and methods
miRNA, mRNA, and protein expression was detected by real-time quantitative polymerase chain reaction and western blot. Cell proliferation was detected by CCK-8 and BrdU assays. The target of miR-590-5p was confirmed by dual-luciferase reporter assay.

Results
MiR-590-5p expression was significantly down-regulated in fetal ASM cells stimulated with PDGF (p < 0.05). Overexpression of miR-590-5p inhibited cell proliferation (p < 0.05), whereas the suppression of miR-590-5p promoted cell proliferation of fetal ASM cells stimulated with PDGF (p < 0.05). Signal transducer and activator of transcription 3 (STAT3) was identified as a target gene of miR-590-5p. In addition, miR-590-5p negatively regulated STAT3 expression (p < 0.05). Moreover, miR-590-5p also modulated downstream genes of STAT3 including cyclin D3 and p27 (p < 0.05). The restoration of STAT3 significantly reversed the inhibitory effect of miR-590-5p on fetal ASM cell proliferation.

Conclusions
MiR-590-5p inhibits proliferation of fetal ASM cells by down-regulating STAT3, thereby suggesting a novel therapeutic target for the treatment of pediatric asthma.

keywords:

airway smooth muscle cells, asthma, miR-590-5p, STAT3

references:
Asher MI, Montefort S, Bjorksten B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multicountry cross-sectional surveys. Lancet 2006; 368: 733-43.
Palmer LJ, Rye PJ, Gibson NA, et al. Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age. Am J Respir Crit Care Med 2001; 163: 37-42.
Majak P, Jerzynska J, Bojo M, et al. Cytokine profiling in exhaled breath condensate after exercise challenge in asthmatic children with post-exercise symptoms. Arch Med Sci 2016; 12: 778-84.
Attanasi M, Consilvio NP, Rapino D, et al. Bronchial hyperresponsiveness to mannitol, airway inflammation and Asthma Control Test in atopic asthmatic children. Arch Med Sci 2016; 12: 137-44.
Barbato A, Turato G, Baraldo S, et al. Airway inflammation in childhood asthma. Am J Respir Crit Care Med 2003; 168: 798-803.
Brown SD, Baxter KM, Stephenson ST, et al. Airway TGF-beta1 and oxidant stress in children with severe asthma: association with airflow limitation. J Allergy Clin Immunol 2012; 129: 388-396, 396 e381-388.
Lin SC, Chou HC, Chiang BL, et al. CTGF upregulation correlates with MMP-9 level in airway remodeling in a murine model of asthma. Arch Med Sci 2017; 13: 670-6.
Martin JG, Ramos-Barbon D. Airway smooth muscle growth from the perspective of animal models. Respir Physiol Neurobiol 2003; 137: 251-61.
Bagga S, Bracht J, Hunter S, et al. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 2005; 122: 553-63.
Adams BD, Parsons C, Walker L, et al. Targeting noncoding RNAs in disease. J Clin Invest 2017; 127: 761-71.
Deshpande DA, Dileepan M, Walseth TF, et al. MicroRNA regulation of airway inflammation and airway smooth muscle function: relevance to asthma. Drug Dev Res 2015; 76: 286-95.
Darnell JE Jr. STATs and gene regulation. Science 1997; 277: 1630-5.
Simeone-Penney MC, Severgnini M, Tu P, et al. Airway epithelial STAT3 is required for allergic inflammation in a murine model of asthma. J Immunol 2007; 178: 6191-9.
Simon AR, Takahashi S, Severgnini M, et al. Role of the JAK-STAT pathway in PDGF-stimulated proliferation of human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2002; 282: L1296-304.
Gavino AC, Nahmod K, Bharadwaj U, et al. STAT3 inhibition prevents lung inflammation, remodeling, and accumulation of Th2 and Th17 cells in a murine asthma model. Allergy 2016; 71: 1684-92.
Shan X, Miao Y, Fan R, et al. MiR-590-5P inhibits growth of HepG2 cells via decrease of S100A10 expression and inhibition of the Wnt pathway. Int J Mol Sci 2013; 14: 8556-69.
Zhou Q, Zhu Y, Wei X, et al. MiR-590-5p inhibits colorectal cancer angiogenesis and metastasis by regulating nuclear factor 90/vascular endothelial growth factor A axis. Cell Death Dis 2016; 7: e2413.
Dai Y, Zhang Z, Cao Y, et al. MiR-590-5p inhibits oxidized-LDL induced angiogenesis by targeting LOX-1. Sci Rep 2016; 6: 22607.
Pandya HC, Snetkov VA, Twort CH, et al. Oxygen regulates mitogen-stimulated proliferation of fetal human airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2002; 283: L1220-30.
Redhu NS, Shan L, Al-Subait D, et al. IgE induces proliferation in human airway smooth muscle cells: role of MAPK and STAT3 pathways. Allergy Asthma Clin Immunol 2013; 9: 41.
Simeone-Penney MC, Severgnini M, Rozo L, et al. PDGF-induced human airway smooth muscle cell proliferation requires STAT3 and the small GTPase Rac1. Am J Physiol Lung Cell Mol Physiol 2008; 294: L698-704.
Ohno I, Nitta Y, Yamauchi K, et al. Eosinophils as a potential source of platelet-derived growth factor B-chain (PDGF-B) in nasal polyposis and bronchial asthma. Am J Respir Cell Mol Biol 1995; 13: 639-47.
Aubert JD, Hayashi S, Hards J, et al. Platelet-derived growth factor and its receptor in lungs from patients with asthma and chronic airflow obstruction. Am J Physiol 1994; 266: L655-63.
Perry MM, Baker JE, Gibeon DS, et al. Airway smooth muscle hyperproliferation is regulated by microRNA-221 in severe asthma. Am J Respir Cell Mol Biol 2014; 50: 7-17.
Hu R, Pan W, Fedulov AV, et al. MicroRNA-10a controls airway smooth muscle cell proliferation via direct targeting of the PI3 kinase pathway. FASEB J 2014; 28: 2347-57.
Liu Y, Yang K, Sun X, et al. MiR-138 suppresses airway smooth muscle cell proliferation through the PI3K/AKT signaling pathway by targeting PDK1. Exp Lung Res 2015; 41: 363-9.
Liu Y, Sun X, Wu Y, et al. Effects of miRNA-145 on airway smooth muscle cells function. Mol Cell Biochem 2015; 409: 135-43.
Chen M, Huang L, Zhang W, et al. MiR-23b controls TGF-beta1 induced airway smooth muscle cell proliferation via TGFbetaR2/p-Smad3 signals. Mol Immunol 2016; 70: 84-93.
Chen M, Shi J, Zhang W, et al. MiR-23b controls TGF-beta1 induced airway smooth muscle cell proliferation via direct targeting of Smad3. Pulm Pharmacol Ther 2017; 42: 33-42.
Cheng W, Yan K, Xie LY, et al. MiR-143-3p controls TGF-beta1-induced cell proliferation and extracellular matrix production in airway smooth muscle via negative regulation of the nuclear factor of activated T cells 1. Mol Immunol 2016; 78: 133-9.
Zhou L, Zhao LC, Jiang N, et al. MicroRNA miR-590-5p inhibits breast cancer cell stemness and metastasis by targeting SOX2. Eur Rev Med Pharmacol Sci 2017; 21: 87-94.
Jiang X, Xiang G, Wang Y, et al. MicroRNA-590-5p regulates proliferation and invasion in human hepatocellular carcinoma cells by targeting TGF-beta RII. Mol Cells 2012; 33: 545-51.
Litonjua AA, Tantisira KG, Lake S, et al. Polymorphisms in signal transducer and activator of transcription 3 and lung function in asthma. Respir Res 2005; 6: 52-61.
Yamasaki A, Saleh A, Koussih L, et al. IL-9 induces CCL11 expression via STAT3 signalling in human airway smooth muscle cells. PLoS One 2010; 5: e9178.
Saleh A, Shan L, Halayko AJ, et al. Critical role for STAT3 in IL-17A-mediated CCL11 expression in human airway smooth muscle cells. J Immunol 2009; 182: 3357-65.
Shan L, Redhu NS, Saleh A, et al. Thymic stromal lymphopoietin receptor-mediated IL-6 and CC/CXC chemokines expression in human airway smooth muscle cells: role of MAPKs (ERK1/2, p38, and JNK) and STAT3 pathways. J Immunol 2010; 184: 7134-43.
Lv J, Sun B, Mai Z, et al. STAT3 potentiates the ability of airway smooth muscle cells to promote angiogenesis by regulating VEGF signalling. Exp Physiol 2017; 102: 598-606.
Yan XT, Ji LJ, Wang Z, et al. MicroRNA-93 alleviates neuropathic pain through targeting signal transducer and activator of transcription 3. Int Immunopharmacol 2017; 46: 156-62.
Liu S, Hu C, Wang Y, et al. miR-124 inhibits proliferation and invasion of human retinoblastoma cells by targeting STAT3. Oncol Rep 2016; 36: 2398-404.
Stout BA, Bates ME, Liu LY, et al. IL-5 and granulocyte-macrophage colony-stimulating factor activate STAT3 and STAT5 and promote Pim-1 and cyclin D3 protein expression in human eosinophils. J Immunol 2004; 173: 6409-17.
Amin HM, McDonnell TJ, Ma Y, et al. Selective inhibition of STAT3 induces apoptosis and G(1) cell cycle arrest in ALK-positive anaplastic large cell lymphoma. Oncogene 2004; 23: 5426-34.
Wang ST, Ho HJ, Lin JT, et al. Simvastatin-induced cell cycle arrest through inhibition of STAT3/SKP2 axis and activation of AMPK to promote p27 and p21 accumulation in hepatocellular carcinoma cells. Cell Death Dis 2017; 8: e2626.
Yu TY, Pang JH, Wu KP, et al. Platelet-rich plasma increases proliferation of tendon cells by modulating Stat3 and p27 to up-regulate expression of cyclins and cyclin-dependent kinases. Cell Prolif 2015; 48: 413-20.
FEATURED PRODUCTS
Quick links
© 2018 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.
PayU - płatności internetowe