Mechanical stretch regulates cell survival in human  bladder smooth muscle cells in vitro

Galvin, David; Watson, R. William G.; Gillespie, James; Brady, Hugh R.; Fitzpatrick, John M.

doi:10.1152/ajprenal.00168.2002

Cited by 41 publications

(36 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Orsola et al 38 reported that cyclic stretch and relaxation of human detrusor SMC led to increased DNA and protein synthesis but apoptosis was not examined. Galvin et al 39 reported similar findings; in addition, apoptosis was decreased with stretch. On the other hand, there are reports that mechanical stretch does lead to increased apoptosis of both vascular smooth muscle 40 and renal epithelial 41 cells.…”

Section: Molecular Correlates Of Increased Apoptosis In Fetal Boomentioning

confidence: 59%

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Thiruchelvam

Nyírády

Peebles

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

During organogenesis, net growth of tissues is determined by a balance between proliferation, hypertrophy, and apoptotic death. Human fetal bladder outflow obstruction is a major cause of end-stage renal failure in children and is associated with complex pathology in the kidney and lower urinary tract. Experimental manipulation of the fetal sheep urinary tract has proved informative in understanding the pathobiology of congenital obstructive uropathy. In this study we used an ovine model of fetal bladder outflow obstruction to examine effects on apoptotic cell death in the developing urinary bladder. While 30 days of obstruction in utero between 75 and 105 days gestation resulted in overall growth of the fetal bladder as assessed by weight, protein, and DNA measurements, we found that apoptosis, as assessed by in situ end-labeling, was up-regulated in fetal bladder detrusor muscle and lamina propria cells and that this was accompanied by a down-regulation of the anti-death protein Bcl-2 and an up-regulation of the pro-death protein Bax. Moreover, activated caspase-3, an effector of apoptotic death, was increased in obstructed bladders. This is the first study to define altered death in an experimental fetal model of bladder dysmorphogenesis. We speculate that enhanced apoptosis in detrusor smooth muscle cells is part of a remodeling response during compensatory hyperplasia and hypertrophy. Conversely, in the lamina propria, an imbalance between death and proliferation leads to a relative depletion of cells.

show abstract

Section: Molecular Correlates Of Increased Apoptosis In Fetal Boomentioning

confidence: 59%

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Thiruchelvam

Nyírády

Peebles

et al. 2003

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…In the mouse, TRPV2 is activated by IGF-1, a cytokine endowed with potent mitogenic and antiapoptotic [25,26] effects on cancer cells [9]; moreover, increased proliferation and survival of human bladder smooth muscle cells induced by mechanical stress is associated with increased IGF-1 levels [27]. Given the high level of IGF-1/IGF-1 receptor (IGF-1R) found in bladder tumours and its role in bladder cancer progression [28], and the strong TRPV2 increase in high-grade and -stage tumours, we would like to suggest that the TRPV2/ IGF-1/IGF-1R pathway plays an important role in the control of UC growth and progression.…”

Section: Discussionmentioning

confidence: 99%

Transient Receptor Potential Vanilloid Type 2 (TRPV2) Expression in Normal Urothelium and in Urothelial Carcinoma of Human Bladder: Correlation with the Pathologic Stage

et al. 2008

View full text Add to dashboard Cite

“…Clinical studies have shown that both hypertrophy and hyperplasia of human airway smooth muscle cells (HASMCs) play key roles in airway remodeling (12)(13)(14)(15)(16). Many lines of evidence have demonstrated that hypertrophy in cardiomyocytes, skeletal myotubes, and smooth muscle cells is induced by various hypertrophic stimuli, including mechanical stretch (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). Recently, it has been shown that miRNAs play important roles in the induction of cardiac hypertrophy as well as response to hypertrophic stimuli (28 -32).…”

Section: Micrornas (Mirnas)mentioning

confidence: 99%

“…Stretch Induces HASMCs Hypertrophy-Accumulating evidences have demonstrated that stretch can induce cardiac, skeletal, and smooth muscle cell hypertrophy (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27). To test this in HASMCs, we stimulated the cells with a 1-h stretch for every 12 h up to 3 days.…”

Section: Mechanical Stretch Up-regulates Mirnas Expression-mentioning

confidence: 99%

Mechanical Stretch Up-regulates MicroRNA-26a and Induces Human Airway Smooth Muscle Hypertrophy by Suppressing Glycogen Synthase Kinase-3β

Mohamed

Lopez

Boriek

2010

Journal of Biological Chemistry

192

154

View full text Add to dashboard Cite

Airway smooth muscle hypertrophy is one of the hallmarks of airway remodeling in severe asthma. Several human diseases have been now associated with dysregulated microRNA (miRNA) expression. miRNAs are a class of small non-coding RNAs, which negatively regulate gene expression at the post-transcriptional level. Here, we identify miR-26a as a hypertrophic miRNA of human airway smooth muscle cells (HASMCs). We show that stretch selectively induces the transcription of miR-26a located in the locus 3p21.3 of human chromosome 3. The transcription factor CCAAT enhancer-binding protein ␣ (C/EBP␣) directly activates miR-26a expression through the transcriptional machinery upon stretch. Furthermore, stretch or enforced expression of miR-26a induces HASMC hypertrophy, and miR-26 knockdown reverses this effect, suggesting that miR-26a is a hypertrophic gene. We identify glycogen synthase kinase-3␤ (GSK-3␤), an anti-hypertrophic protein, as a target gene of miR-26a. Luciferase reporter assays demonstrate that miR-26a directly interact with the 3-untranslated repeat of the GSK-3␤ mRNA. Stretch or enforced expression of miR-26a attenuates the endogenous GSK-3␤ protein levels followed by the induction of HASMC hypertrophy. miR-26 knockdown reverses this effect, suggesting that miR-26a-induced hypertrophy occurs via its target gene GSK-3␤. Overall, as a first time, our study unveils that miR-26a is a mechanosensitive gene, and it plays an important role in the regulation of HASMC hypertrophy. MicroRNAs (miRNAs)2 are an evolutionarily conserved novel class of small non-coding RNAs that have achieved status as potent regulators of gene expression. According to their genomic location relative to protein-coding gene locus, miRNAs can be divided into intergenic miRNAs and intragenic miRNAs. The former have independent transcriptional units, including promoter, transcript sequence, and terminator; therefore, they do not overlap with other genes (1, 2). The later are found in the introns of protein-coding host genes, and they generally share the same regulatory motifs with their host genes (3-5). Most of the miRNAs are transcribed by RNA polymerase II as primary miRNAs (1, 2) and processed by the RNase III enzymes Drosha and Dicer to produce 21-to 23-nucleotide double-stranded RNA duplexes (6, 7). These smaller RNAs are then exported to the cytoplasm by Exportin 5 (8, 9), where they are subsequently processed into mature miRNAs by Dicer. The mature miRNAs are loaded into the miRNA-induced silencing complex (7), where they recognize their target protein-coding mRNAs to inhibit mostly mRNA translation or degradation (10) by base pairing to complementary sequences within the 3Ј-untranslated region (3Ј UTR). With respect to miRNAs functions, they play pivotal roles in the pathophysiological processes such as apoptosis, cell differentiation, cell proliferation, and organ development (4, 11). Functionally speaking, several human diseases have now been associated with dysregulated miRNAs expression.Airway remodeling is a characteristic featu...

show abstract

Mechanical stretch regulates cell survival in human bladder smooth muscle cells in vitro

Cited by 41 publications

References 22 publications

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Urinary Outflow Obstruction Increases Apoptosis and Deregulates Bcl-2 and Bax Expression in the Fetal Ovine Bladder

Transient Receptor Potential Vanilloid Type 2 (TRPV2) Expression in Normal Urothelium and in Urothelial Carcinoma of Human Bladder: Correlation with the Pathologic Stage

Mechanical Stretch Up-regulates MicroRNA-26a and Induces Human Airway Smooth Muscle Hypertrophy by Suppressing Glycogen Synthase Kinase-3β

Contact Info

Product

Resources

About