Loss of Matrix Metalloproteinase-2 Amplifies Murine Toxin-Induced Liver Fibrosis by Upregulating Collagen I Expression

Abstract

Background and Aims-Matrix metalloproteinase-2 (MMP-2), a type IV collagenase secreted by activated hepatic stellate cells (HSCs), is upregulated in chronic liver disease and is considered a profibrotic mediator due to its proliferative effect on cultured HSCs and ability to degrade normal liver matrix. Although associative studies and cell culture findings suggest that MMP-2 promotes hepatic fibrogenesis, no in vivo model has definitively established a pathologic role for MMP-2 in the development and progression of liver fibrosis. We therefore examined the impact of MMP-2 deficiency on liver fibrosis development during chronic CCl 4 liver injury and explored the effect of MMP-2 deficiency and overexpression on collagen I expression.

Metalloproteinases in liver fibrosis: current insights

“…53,54 Thus, MMP-2-deficient mice show enhanced fibrosis after CCL 4 treatment and MMP-2 could be therefore critical for inhibiting type I collagen synthesis by activated HSCs, which strongly express this MMP. 55,56 MMP-9 and MMP-2 are elevated in serum and livers of patients with chronic hepatitis type B and C. [57][58][59] Elevated expression of MMPs in the mentioned fibrotic conditions was shown both in liver parenchyma 60 and portal macrophages. 57,61 Especially, MMP-9 seems to be involved in ongoing liver inflammation, 62 and its level drops after antiviral treatment.…”

Anatomy, pathophysiology and basic mechanisms of disease

“…In the liver, activated stellate cells are a key source of this enzyme. 618,619 Three stromelysins (MMP-3, MMP-10, MMP-11) and a closely related metalloproteinase, PUMP-1, have been identified from a variety of tissues. These enzymes have a broad range of matrix degradation activity.…”

Effects of RNAi-Mediated Matrix Metalloproteinase-2 Gene Silencing on the Invasiveness and Adhesion of Esophageal Carcinoma Cells, KYSE150

“…During this step, MMPs are believed to play important roles [13]. MMP-2 is a subgroup of the MMPs, also known as gelatinases A, which is believed to have functions in the progression and invasion of tumors [14] and other benign diseases [15,16]. Previous studies indicate that the overexpression of MMP-2 was observed in several kinds of cancers, including pancreatic cancer [17], breast cancer [18], and lung cancer [19].…”