Expression of tissue inhibitor of matrix metalloproteinases-1 during aging in rat liver

Abstract

To investigate the expression and role of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) during natural aging in rat liver and to detect the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9. The rats were divided into 3-mo-old group (n = 5), 10-mo-old group (n = 5) and 24-mo-old group (n = 5). Histopathologic changes of liver were observed with HE and Masson stain. The location and protein expressions of TIMP-1 were determined by immunohistochemistry and Western blot; message RNA (mRNA) levels were measured in livers from rats of various ages by semi-quantitative reverse transcriptional polymerase chain reaction (RT-PCR). In addition, the expression of MMP-2 and MMP-9 was assessed by RT-PCR and Western blot. Histologic examination showed that the aging liver had excessive fatty degeneration and collagen deposition. Immunohistochemical staining showed that TIMP-1 related antigen in livers was located in cytoplasm. The protein expression of TIMP-1 was significantly higher in the oldest animals and the mRNA expression was increased significantly in the 24-mo-old rats (t = 4.61, P = 0.002<0.05, 24-vs 10-mo-old rats; t = 4.31, P = 0.003<0.05, 24- vs 3-mo-old rats). The expression of MMP-2 and MMP-9 had no change during aging; the ratios TIMP-1/MMP-2 and TIMP-1/MMP-9 in aging liver were significantly higher than those in maturation and young livers. TIMP-1 may play an important role in the process of liver aging.