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

Arch Biochem Biophys. 2014 Dec 15:564:197-202. doi: 10.1016/j.abb.2014.09.012. Epub 2014 Sep 28.

Abstract

Mechanical stimulation is an essential factor for organisms to develop normally. In bladder development matrix metalloproteinases (MMPs) play an important role through structure remodeling and regulating the cell proliferation. In this study, we investigated the simulated physiological stretch induced proliferation of HBSMCs; MMPs/TIMPs expression in stretch and non-stretch groups. HBSMCs were exposed to cyclic stretch with defined parameters (5%, 10% and 15% elongation). The expression of MMPs and TIMPs in each parameter and non-stretch groups was examined at the transcriptional and translational levels respectively. 5-Ethynyl-2'-deoxyuridine (EdU) assay was used to assess cell proliferation. In the presence of the broad spectrum MMPs inhibitor (Batimastat), cells proliferation, MMPs and tissue inhibitors of metalloproteinases (TIMPs) expression were assessed again. Compared with non-stretch group, HBSMCs in stretch groups showed higher proliferation. The expression of MMP-1, 2, 3, 7 was up-regulated in stretch groups, and it remained at the same high level in 10% and 15% stretch groups. TIMP-1, 2 expression only increased under 15% stretch. Stretch resulted in elevated cell proliferation was abolished by Batimastat. In conclusion, the proliferation of HBSMCs induced by stretch was resulted from the stretch-induced MMPs expression and release.

Keywords: Cell proliferation; Matrix metalloproteinases; Smooth muscle cell; Stretch; Urinary bladder.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology*
  • Cells, Cultured
  • Collagenases / biosynthesis*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Gene Expression Regulation, Enzymologic / physiology*
  • Humans
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / enzymology*
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / pharmacology
  • Protease Inhibitors / pharmacology
  • Thiophenes / pharmacology
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*
  • Urinary Bladder

Substances

  • Protease Inhibitors
  • TIMP1 protein, human
  • TIMP2 protein, human
  • Thiophenes
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Phenylalanine
  • batimastat
  • Collagenases