Collagen I is expressed by hepatocytes through activation of AIM2/ASC/caspase-1 signaling pathway

Abstract

Abstract Background Liver fibrosis is the result of diffuse excessive deposition of extracellular matrix (ECM) in liver. Collagen is the main component of extracellular matrix. Absent in melanoma 2 (AIM2) is involved in the formation of inflammsome and plays an important role in inflammatory response. However, it is unclear whether AIM2 is involved in the pathogenesis of liver fibrosis. In the present study, we explored the role of AIM2 in the expression of collagen I. Methods In this study, AIM2 was used to co-culture with HepG2 cells. Cell counting kit-8 (CCK-8) was used to measure cell viability. Real time-quantitative PCR (RT-qPCR) and Western blotting were used to detect collagen I expression at mRNA or protein level, respectively. Then HepG2 cells were treated with caspase activation recruitment domain (ASC), pcDNA(+)-AIM2, small interfering RNA (siRNA) and Z-YVAD-fluoromethylketone (Z-YVAD-FMK) to explore their roles in collagen I expression, respectively. Results The viability of HepG2 cells could be not affected with the increased concentrations of AIM2 and Z-YVAD-FMK. The filamentous prisms and vacuoles of HepG2 cells became more obvious when the concentrations of AIM2 increased to 80ng/ml. The expression level of collagen I increased with the increased concentrations of AIM2. The expression level of collagen I could be also induced by pcDNA(+)-AIM2 vector. The expression level of collagen I could be inhibited by ASC siRNA and Z-YVAD-FMK, respectively. Conclusion Collagen I expression could be induced by AIM2 through ASC/caspase-1 signaling pathway. AIM2 might be involved in the pathogenesis of liver fibrosis through inducing collagen I expression.