Spatiotemporal expression of matrix metalloproteinase-1 in progression of nonalcoholic steatohepatitis
Journal Title: Journal of Modern Human Pathology - Year 2016, Vol 1, Issue 2
Abstract
Human matrix metalloproteinase-1 (MMP-1) has been shown to contribute to the regression of experimental liver fibrosis when ectopically expressed in rodents. It remains unknown whether the same mechanism exists in chronic liver diseases in humans. This study was conducted to elucidate the functional contribution of MMP-1 to the pathophysiology of nonalcoholic steatohepatitis (NASH). Samples from 19 histologically proven NASH patients were examined together with normal liver specimens from four subjects. Expression of MMP-1, caveolin-1, active and latent forms of TGF-β, and type 1 procollagen was analyzed using immunohistochemical, western blotting and immunoelectron microscopic (IEM) examinations. In the early stage of NASH, MMP-1 was expressed predominantly in Kupffer cells and monocytes. Remarkable expression of MMP-1 and caveolin-1 was observed in hepatic progenitor cells (HPCs), hepatic stellate cells (HSC) and proliferating capillary endothelial cells in the advanced stage of NASH. MMP-1 immunostaining was significantly greater in advanced (p < 0.014) and early (p < 0.016) NASH than in control. IEM revealed MMP-1-immunoreactive products in HPCs/HSC/small hepatocytes. Active form of TGF-β and type I procollagen were detected at the edge of those capillary endothelial cells adjacent to the HPCs. MMP-1 expressed in HPCs/small hepatocytes/ capillary endothelial cells may contribute, at least in part, to the repair and regeneration of fibrotic liver through the caveolin-1 signal in the advanced stage of NASH.
Authors and Affiliations
Yokomori H, Inagaki Y, Ando W, Hara M, Komiyama T, Kojima S, Oda M, Kuroda H, Suzuki Y, Okazaki I
Keywords
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- EP ID EP553249
- DOI 10.14312/2397-6845.2016-3
- Views 63
- Downloads 0
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