Enhanced expression of heat shock protein 47 in rat model of peritoneal fibrosis.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mishima
Yoko
Y
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Miyazaki
Masanobu
M
Abe
Katsushige
K
Ozono
Yoshiyuki
Y
Shioshita
Kei
K
Xia
Zhiyin
Z
Harada
Takashi
T
Taguchi
Takashi
T
Koji
Takehiko
T
Kohno
Shigeru
S
D000818:Animals; D002710:Chlorhexidine / Q000031:analogs & derivatives*; D018450:Disease Progression; D024022:Fibrillar Collagens / Q000378:metabolism; D005355:Fibrosis / Q000209:etiology* / Q000378:metabolism*; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D010529:Peritoneal Cavity / Q000473:pathology* / Q000503:physiopathology*; D010531:Peritoneal Dialysis, Continuous Ambulatory / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D024022:Fibrillar Collagens; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494662:Serpinh1 protein, rat; C010882:chlorhexidine gluconate; D002710:Chlorhexidine