Fibrosis and matrix metalloproteinases in rat renal allografts.
The temporal activity and gene expression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase (TIMP) were investigated in a rat model of chronic allograft nephropathy. Gelatinolytic activity of MMP-2 and -9 were demonstrated by zymography, and MMP-2,-9 and TIMP-3 mRNA by in situ hybridization. The generation of fibrosis was determined as total collagen content/DNA. Significantly more latent and active MMP-2, as well as latent MMP-9, were seen in allografts than in autografts. Intense MMP-2 mRNA expression was demonstrated in the allografts during the first 20 days after transplantation, located mainly in the interstitium of the kidney. In addition, some tubular cells expressed MMP-2 mRNA. After day 20, MMP-2 gene expression was faint. MMP-9 mRNA expression in allografts was located mainly in the glomerulus. TIMP-3 mRNA expression was downregulated in allografts. MMP-2, MMP-9 and TIMP-3 seem to play a critical role in the development of fibrosis in the renal allograft.
Inkinen
Kaija A
KA
Transplant Unit Research Laboratory, Department of Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. kaija.inkinen@hus.fi
Soots
Anu P
AP
Krogerus
Leena A
LA
Lautenschlager
Irmeli T
IT
Ahonen
Juhani P
JP
D000818:Animals; D003094:Collagen / Q000096:biosynthesis; D005355:Fibrosis; D015870:Gene Expression; D017403:In Situ Hybridization; D016030:Kidney Transplantation / Q000473:pathology* / Q000502:physiology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D011919:Rats, Inbred Strains; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous
D012333:RNA, Messenger; D019717:Tissue Inhibitor of Metalloproteinase-3; D003094:Collagen; D045726:Metalloproteases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9