Differential expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in thioacetamide-induced chronic liver injury.
Hepatic fibrogenesis, a complex process that involves a marked accumulation of extracellular matrix components, activation of cells capable of producing matrix materials, cytokine release, and tissue remodeling, is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The MMP-TIMP balance can regulate liver fibrogenesis. The aim of this study was to evaluate the expression patterns of MMPs and TIMPs during thioacetamide (TAA)-induced liver fibrogenesis. Chronic liver injury was induced with TAA (200 mg/kg i.p.) for 4 or 7 weeks in male Sprague-Dawley rats. Hepatic injury and fibrosis were assessed by hematoxylin-eosin (H&E) staining, and collagen deposition was confirmed by Sirius Red staining. The level of hepatic injury was quantified by serological analysis. The transcriptional and translational levels of alpha-smooth muscle actin (alpha-SMA), MMPs, and TIMPs in the liver were measured by Western blotting, RT-PCR, and immunohistochemistry. MMP, TIMP, and alpha-SMA were observed along fibrotic septa and portal spaces around the lobules. TAA treatment increased transcription of both MMPs and TIMPs, but only TIMPs showed increased translation. The dominant expression of TIMPs may regulate the function of MMPs to maintain liver fibrosis induced by TAA.
Park
Soo Young
SY
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
Shin
Hye Won
HW
Lee
Kyoung Bun
KB
Lee
Min-Jae
MJ
Jang
Ja-June
JJ
D000818:Animals; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000633:toxicity*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism*
D019714:Tissue Inhibitor of Metalloproteinases; D013853:Thioacetamide; D003094:Collagen; D020782:Matrix Metalloproteinases