Significance of MMP-2 and TIMP-2 mRNA expressions on glomerular cells in the development of glomerulosclerosis.
OBJECTIVE
To study the expressions of MMP-2 and TIMP-2 mRNA on cultured rat mesangial cells (MsC) and in human diseased glomeruli, and to explore their significance in the development of glomerulosclerosis.


METHODS
The expressions of MMP-2, TIMP-2, and Col IV mRNA on cultured rat MsC stimulated by IL-1 or/and TGF-beta1 were investigated through Northern blot analysis. The levels of MMP-2 and TIMP-2 mRNA expressions and immunoreactivity of PCNA and Col IV in human diseased glomeruli from renal biopsies of lupus nephritis (LN) patients were examined by in situ hybridization and immunohistochemistry, respectively.


RESULTS
The levels of MMP-2, TIMP-2, and Col IV mRNA expressions were markedly increased on cultured rat MsC stimulated by IL-1 or/and TGF-beta1. Meanwhile, upregulation of MMP-2 and TIMP-2 mRNA expressions was confirmed in diseased glomeruli from patients with various subtypes of LN, and was closely related to the positive cell number of PCNA presentation and deposition of Col IV in glomeruli.


CONCLUSIONS
The results suggest that the over-expressions of MMP-2 and TIMP-2 mRNA on glomerular cells might play a critical role in the development of glomerulosclerosis.
Zhang
Zhi-Gang
ZG
Department of Pathology, Shanghai Medical College of Fudan University, Shanghai 200032.
Liu
Xue-Guang
XG
Chen
Guang-Ping
GP
Zhang
Xiu-Rong
XR
Guo
Mu-Yi
MY
D000818:Animals; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000096:biosynthesis / Q000235:genetics; D005920:Glomerular Mesangium / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D008181:Lupus Nephritis / Q000378:metabolism* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D024141:Collagen Type IV; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2