Recombinant GPI-anchored TIMP-1 stimulates growth and migration of peritoneal mesothelial cells.

PloS One
Roghieh DjafarzadehPeter J Nelson

Abstract

Mesothelial cells are critical in the pathogenesis of post-surgical intraabdominal adhesions as well as in the deterioration of the peritoneal membrane associated with long-term peritoneal dialysis. Mesothelial denudation is a pathophysiolocigally important finding in these processes. Matrix metalloproteinase (MMP) biology underlies aspects of mesothelial homeostasis as well as wound repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) moderate MMP activity. By modifying human TIMP-1 through the addition of a glycosylphosphatidylinositol (GPI) anchor, a recombinant protein was generated that efficiently focuses TIMP-1 on the cell surface. Treatment of primary mesothelial cells with TIMP-1-GPI facilitates their mobilization and migration leading to a dramatic increase in the rate of wound experimental closure. Mesothelial cells treated with TIMP-1-GPI showed a dose dependent increase in cell proliferation, reduced secretion of MMP-2, MMP-9, TNF-α and urokinase-type plasminogen activator (uPA), but increased tissue plasminogen activator (t-PA). Treatment resulted in reduced expression and processing of latent TGF-β1. TIMP-1-GPI stimulated rapid and efficient in vitro wound closure. The agent enhanced mesothelial...Continue Reading

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Citations

May 2, 2014·Biochemical Pharmacology·Francis G Spinale, Francisco Villarreal
Sep 11, 2014·Journal of Cancer Research and Therapeutics·Fengtan Li, Weisan Zhang
Oct 26, 2012·The Journal of Investigative Dermatology·Roghieh DjafarzadehPeter J Nelson
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Dec 26, 2015·Journal of Cardiovascular Pharmacology and Therapeutics·Michelle Lizotte-WaniewskiCharles H Hennekens

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