EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Hypoxia-increased expression of genes involved in inflammation, dedifferentiation, pro-fibrosis, and extracellular matrix remodeling of human bladder smooth muscle cells



Hypoxia-increased expression of genes involved in inflammation, dedifferentiation, pro-fibrosis, and extracellular matrix remodeling of human bladder smooth muscle cells



In Vitro Cellular & Developmental Biology. Animal (): -



NlmCategory="UNASSIGNED">Partial bladder outlet obstruction (pBOO) is characterized by exaggerated stretch, hydrodynamic pressure, and inflammation which cause significant damage and fibrosis to the bladder wall. Several studies have implicated hypoxia in its pathophysiology. However, the isolated progressive effects of hypoxia on bladder cells are not yet defined. Sub-confluent normal human bladder smooth muscle cells (hbSMC) were cultured in 3% O2 tension for 2, 24, 48, and 72 h. RNA, cellular proteins, and secreted proteins were used for gene expression analysis, immunoblotting, and ELISA, respectively. Transcription of hypoxia-inducible factor (HIF)1α and HIF2α were transiently induced after 2 h of hypoxia (p < 0.05), whereas HIF3 was upregulated after 72 h (p < 0.005). HIF1 and HIF3α proteins were significantly induced after 2 and 72 h, respectively. VEGF mRNA increased significantly after 24 and 72 h (p < 0.005). The inflammatory cytokines, TGFB (protein and mRNA), IL 1β, 1L6, and TNFα (mRNA) demonstrated a time-dependent increased expression. Furthermore, the anti-inflammatory cytokine IL-10 was downregulated after 72 h (p < 0.05). Evidence of smooth muscle cell dedifferentiation included increased αSMA, vimentin, and desmin. Evidence of pro-fibrotic changes included increased CTGF, SMAD 2, and SMAD 3 as well as collagens 1, 2, 3, and 4, fibronectin, aggrecan, and TIMP 1 transcripts (p < 0.05). Total collagen proteins also increased time-dependently (p < 0.05). Together, these results show that exposure of hbSMC to low oxygen tension results in intense hypoxic cascade, including inflammation, de-differentiation, pro-fibrotic changes, and increased extracellular matrix expression. This elucidates mechanisms of hypoxia-driven bladder deterioration in bladder cells, which is important in tailoring in vivo experiments and may ultimately translate into improved clinical outcomes.

(PDF emailed within 0-6 h: $19.90)

Accession: 058028554

Download citation: RISBibTeXText

PMID: 27632054

DOI: 10.1007/s11626-016-0085-2



Related references

Eosinophils enhance WNT-5a and TGF-β1 genes expression in airway smooth muscle cells and promote their proliferation by increased extracellular matrix proteins production in asthma. Bmc Pulmonary Medicine 16(1): 94-94, 2017

Mammalian target of rapamycin (mTOR) induces proliferation and de-differentiation responses to three coordinate pathophysiologic stimuli (mechanical strain, hypoxia, and extracellular matrix remodeling) in rat bladder smooth muscle. American Journal of Pathology 176(1): 304-319, 2010

Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein. Arteriosclerosis, Thrombosis, and Vascular Biology 21(7): 1146-1151, 2001

Simulated physiological stretch increases expression of extracellular matrix proteins in human bladder smooth muscle cells via integrin α4/αv-FAK-ERK1/2 signaling pathway. World Journal of Urology 35(8): 1247-1254, 2016

Stretch versus contraction of bladder smooth muscle cells evokes contrasting extracellular matrix gene expression and extracellular regulated kinase activation. Journal of Urology 165(5 Supplement): 145, 2001

Smooth muscle alpha-actin and calponin expression and extracellular matrix production of human coronary artery smooth muscle cells in 3D scaffolds. Tissue Engineering. Part A 15(10): 3001-3011, 2009

Fatty acids modulate the composition of extracellular matrix in cultured human arterial smooth muscle cells by altering the expression of genes for proteoglycan core proteins. Diabetes 48(3): 616-622, 1999

Extracellular matrix and nuclear localization of βig-h3 in human bladder smooth muscle and fibroblast cells. Journal of Cellular Biochemistry 79(2): 261-273, 2000

Phenotypic differentiation of human intestinal smooth muscle cells induced by chronic inflammation Increased expression of smooth muscle-specific proteins in vitro. Molecular Biology of the Cell 7(SUPPL ): 539A, 1996

Extracellular matrix and nuclear localization of beta ig-h3 in human bladder smooth muscle and fibroblast cells. Journal of Cellular Biochemistry 79(2): 261-273, 2000

Mechanical stretch of bladder smooth muscle cells in vitro reverses RHAMM and erk mediated extracellular matrix gene expression. Journal of Urology 165(5 Supplement): 144-145, 2001

The induction of nitric oxide synthase in human bladder smooth muscle cells by inflammation A potential mechanism for fibrosis. Pediatrics 104(3 PART 3): 831-832, Sept, 1999

Extracellular matrix gene expression by human endothelial and smooth muscle cells. Matrix 11(6): 380-387, 1991

Identification and regulation of human N-acetylglucosamine deaminase in vascular smooth muscle cells Potential novel mechanism involved in extracellular matrix metabolism. Circulation 96(8 SUPPL ): I549, 10/21/97, 1997

Roles of the ERK1/2 and PI3K/PKB signaling pathways in regulating the expression of extracellular matrix genes in rat pulmonary artery smooth muscle cells. Acta Cirurgica Brasileira 32(5): 350-358, 2017