Figure 1 | Scientific Reports

Figure 1

From: Inhibition of intrahepatic monocyte recruitment by Cenicriviroc and extracellular matrix degradation by MMP1 synergistically attenuate liver inflammation and fibrogenesis in vivo

Figure 1

Schematic showing the pathogenesis of liver fibrosis, and the combination treatment strategy (Cenicriviroc and Matrix Metalloproteinase 1, MMP1) to promote the resolution of liver fibrosis. During liver injury, injured hepatocytes secrete pro-inflammatory factors that activate liver resident Kupffer cells (KCs). Damaged hepatocytes and KCs secrete chemokines especially CCL2 that induces recruitment of CCR2-expressing monocytes via CCL2-CCR2 axis. Following recruitment, monocytes differentiate into macrophages referred to as monocytes-derived macrophages (MoMFs). KCs and MoMFs secrete pro-fibrogenic factors such as transforming growth factor beta (TGF-β) that activates hepatic stellate cells (HSCs). Activated HSCs stimulate monocyte recruitment by secreting CCL2 and produce excessive amounts of extracellular matrix proteins primarily collagen that leads to fibrosis development. Cenicriviroc (CVC, a CCR2/CCR5 antagonist) inhibits monocyte recruitment and thereby blunts TGF-β secretion and HSCs activation which further inhibit monocyte recruitment. MMP1 degrades collagen-rich ECM thereby inhibits HSCs activation and monocyte recruitment. The combination of CVC and MMP1 can potentially contribute to fibrosis resolution.

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