Purpose: It is unknown how bladder smooth muscle cells sense extrinsic mechanical stimuli. The integrins are a large versatile family of transmembrane mechanoreceptors that transduce extracellular matrix (ECM) alterations into the cell, thereby, regulating proliferation, differentiation and ECM synthesis. To our knowledge we provide the first evidence that the integrins may be involved in responses to whole bladder distention and bladder smooth muscle cell stretch.Materials and Methods: Bladders from 100 to 120 gm. rats were stretched to 40 cm. H 2 O for 5 minutes. Five to 96 hours after distention whole bladder mRNAs were isolated for analysis of temporal expression of collagen and integrin genes. Separately quiescent primary culture bladder smooth muscle cells from 1-day-old Sprague-Dawley rats were stretched cyclically for 4 hours. Relative expression of select integrin subunit mRNAs was assessed by semiquantitative reverse transcriptase-polymerase chain reaction. Integrin blockade with asparagine-glycinearginine peptides was used to determine the role of integrins in stretch induced proliferation and the cell cycle in bladder smooth muscle cells.Results: Within 24 hours bladder distention stimulated collagen expression 2-fold (type I) and 5-fold (type III). Collagen levels beyond 24 hours were 8-fold (type I) and 2-fold (type III) greater than in controls, revealing an inverse temporal type I-to-III ratio beyond 24 hours. Coordinate alterations were observed in integrin and collagen expression. In vitro bladder smooth muscle cell integrin 1, 3 and ␣v subunit expression was increased by mechanical stretch 2.5, 3.8 and 5-fold, respectively, while ␣1 expression decreased. Asparagine-glycine-arginine peptide inhibition of integrin function significantly inhibited stretch induced bladder smooth muscle cell proliferation and exit from the G2/M phase of the cell cycle.Conclusions: To our knowledge these results demonstrate for the first time that that bladder distention initiates dynamic alterations in ECM expression. The ability of integrin blockade to suppress stretch induced bladder smooth muscle cell proliferation and the coordinate changes in bladder ECM and integrin expression suggest that integrins mediate key responses to mechanical stimuli in the bladder. Furthermore, cell cycle analysis of resting and stretched bladder smooth muscle cells revealed novel avenues for the examination of integrin and stretch regulation of bladder smooth muscle cell growth.KEY WORDS: bladder; muscle, smooth; rats, Sprague-Dawley; extracellular matrix; integrins To our knowledge the mechanisms regulating bladder smooth muscle cell responses to mechanical stimuli are unknown. Clinically short circuiting prolonged bladder distention by intermittent catheterization is a urological axiom for managing bladders damaged by obstructive uropathy, neurological impairment or voiding abnormalities. 1 This practice underscores the belief that excessive stretch or prolonged distention are key factors driving recognized fibroprolife...
To our knowledge these results demonstrate for the first time that that bladder distention initiates dynamic alterations in ECM expression. The ability of integrin blockade to suppress stretch induced bladder smooth muscle cell proliferation and the coordinate changes in bladder ECM and integrin expression suggest that integrins mediate key responses to mechanical stimuli in the bladder. Furthermore, cell cycle analysis of resting and stretched bladder smooth muscle cells revealed novel avenues for the examination of integrin and stretch regulation of bladder smooth muscle cell growth.
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