Increased proliferation of human bladder smooth muscle cells is mediated by physiological cyclic stretch via the PI3K-SGK1-Kv1.3 pathway

Abstract

It is well known that specific mechanical stimuli induce positive changes in the physiological function and status of a number of cell types. However, an in‑depth understanding of the application of mechanical forces has yet to be developed. The aim of the present study was to explore the optimal elongation and frequency of stretch‑induced proliferation of human bladder smooth muscle cells (HBSMCs) and to investigate the mechanism involved in this process. HBSMCs were seeded in a silicone membrane and subjected to cyclic stretch of 2.5, 5, 10 and 15% equibiaxial elongation at frequencies of 0.05, 0.1, 0.2, 0.5 and 1 Hz, respectively. Bromodeoxyuridine (BrdU) assays were used to detect the proliferative activity of each group. To further determine the mechanism of the cell proliferation process triggered by physiological cyclic stretch, the expression of PI3K/SGK1/Akt/Kv1.3 was investigated at the transcriptional and translational levels by RT‑PCR and western blot analysis, respectively. Optimal physiological stretch was established as 5% elongation at a frequency of 0.1 Hz, whereby HBSMCs revealed a marked increase in proliferative activity compared with the other groups, including the non‑stretched group, which served as the control (P<0.05). The expression of PI3K/SGK1/Kv1.3; however, not Akt, were upregulated by cyclic stretch as compared with the control group. When separately treated with inhibitors of SGK1 and Kv1.3, increased stretch‑induced proliferation was largely eliminated. These results markedly indicate that cyclic stretch induces the proliferation of HBSMCs and the PI3K‑SGK1‑Kv1.3 pathway is involved in this process, either fully or at least partially, rather than its related pathway, PI3K‑Akt.

Periodic Mechanical Stress Activates PKCδ-Dependent EGFR Mitogenic Signals in Rat Chondrocytes via PI3K-Akt and ERK1/2

“…PI3K-Akt signals could respond to mechanical stimuli and modulate proliferation in several nonchondrocytic cell types [28,29]. This study investigated and considered PI3K-Akt signals to be candidate signals for inducing chondrocyte proliferation by periodic [30,31].…”

Regulation of 130-kDa Smooth Muscle Myosin Light Chain Kinase Expression by an Intronic CArG Element

“…This conclusion should, however, be viewed with caution because it is possible that the alterations in proliferation are secondary to impaired contractility. In vascular, airway, and bladder smooth muscle, mechanical strain can induce smooth muscle cell proliferation (45)(46)(47). A decreased mechanical stimulus in CArG knock-out mice may thus also impair intestinal smooth muscle cell proliferation, resulting in attenuated intestinal elongation.…”

Simulated physiological stretch-induced proliferation of human bladder smooth muscle cells is regulated by MMPs

“…Our earlier findings showed that simulated physiological stretch could induce proliferation of HBSMCs through several signaling pathways [11,28]. However, microenvironment changes that affect cell behaviors of HBSMCs under physiological stretch are not well understood.…”