Enhanced Expression of Heat Shock Protein 47 in Rat Model of Peritoneal Fibrosis

Abstract

Peritoneal fibrosis is one of the serious complications of continuous ambulatory peritoneal dialysis therapy and is characterized by collagen accumulation. Heat shock protein 47 (HSP-47) is a collagen-specific molecular chaperon and is closely associated with collagen synthesis; however, the involvement of HSP-47 in the progression of peritoneal fibrosis is not fully understood. To examine the serial pathological alterations caused by peritoneal fibrosis, we made an experimental model of peritoneal fibrosis by daily intraperitoneal injection of chlorhexidine gluconate (CG) in rats for 28 days and examined the expression of HSP-47 together with that of types I and III collagen, alpha-smooth muscle actin (aSMA), and ED-1 (a marker for macrophages) using immunohistochemistry. Rats treated with saline containing 15% ethanol were used as the control group. In the control group, the peritoneal tissue was slightly thickened and HSP-47 was expressed in the peritoneum at day 28. In the CG group, the peritoneal tissue serially became thickened and fibrotic. The expression of HSP-47 was evident in mesothelial cells and submesothelial connective tissue after day 7 of treatment with CG, and increased thereafter. The expression of types I and III collagen and aSMA was proportionally strengthened during our experiments. ED-1-positive cells were present in thickened areas with abundant proliferation of collagen fiber. The number of cells positive for ED-1 increased gradually and reached a maximum at day 21. Our results indicate that, in a rat experimental model of peritoneal fibrosis, the expression of HSP-47 is associated with the progression of peritoneal fibrosis.