Alterations in proteoglycan components and histopathology of the peritoneum in uraemic and peritoneal dialysis (PD) patients.
BACKGROUND
Proteoglycans (PGs) are dominant extracellular matrices (ECMs) in the peritoneal tissues. Human peritoneal mesothelial cells synthesize small proteoglycans including decorin. Peritonitis and long-term peritoneal dialysis (PD) cause fibrotic changes in the peritoneum that result in ECM remodelling and PG synthesis.


METHODS
Twenty-five peritoneal tissues from eight patients at initiation of PD, five long-term PD (>6 years) patients with severe peritonitis lasting for almost 1 month, nine patients after long-term PD (>6 years) without peritonitis and three normal subjects were included in the present study. Expressions of decorin, versican, hyaluronan, MMP-2, alfa smooth muscle actin (alphaSMA) and CD68 for macrophages in these specimens were examined by immunohistochemical staining.


RESULTS
Although expression of decorin was detected in normal subjects, it was markedly decreased with long-term PD treatment. In long-term PD patients, the expression of versican was observed in their fibrotic-thickened peritoneum. Versican was present in fibrous regions, elastic lamina of the peritoneum, vascular walls and perivascular regions. Hyaluronan was observed in the whole thickened peritoneum, but its distribution differed in part from that of versican. MMP-2 was mainly observed around the blood vessels. Alfa SMA-positive cells, namely 'myofibroblasts' and CD68-positive cells, i.e. macrophages, were observed in the fibrotic-thickened peritoneum of long-term PD patients. Expressions of MMP-2, hyaluronan, SMA and CD68 in the peritoneum were marked in long-term PD patients' samples, which were strongly immunostained by versican, and were especially high in peritonitis patients.


CONCLUSIONS
It appears that alterations in PGs, including marked induction of versican with peritonitis and disappearance of decorin, are involved in peritoneal remodelling in PD patients. Versican expression was closely related to the appearance of myofibroblasts and macrophages. These observations suggest that the alteration in PG components following PD therapy and severe inflammation contribute to fibrous thickening of the peritoneum.
Osada
Shiwori
S
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Hamada
Chieko
C
Shimaoka
Tetsutaro
T
Kaneko
Kayo
K
Horikoshi
Satoshi
S
Tomino
Yasuhiko
Y
D000199:Actins / Q000032:analysis; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D008875:Middle Aged; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000737:chemistry* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis*; D014511:Uremia / Q000378:metabolism* / Q000473:pathology; D053675:Versicans / Q000032:analysis; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D058575:Decorin; D016326:Extracellular Matrix Proteins; D006820:Hyaluronic Acid; D020778:Matrix Metalloproteinase 2; D011509:Proteoglycans; D053675:Versicans; C541116:ACTA2 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C546878:DCN protein, human; C508322:VCAN protein, human