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 1Hz, 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 0.1Hz, 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.