Downregulation of IGFBP7 Alleviates LPS-induced Inflammation and Apoptosis in WI-38 Cells via Enhancing Mitophagy.

Abstract

Pediatric pneumonia is an inflammatory disease with a very high incidence. IGF binding protein 7 (IGFBP7) plays an important role in inflammatory diseases. However, the role of IGFBP7 in pediatric pneumonia and its mechanism have not been reported. Human embryonic lung (WI-38) cells were induced by lipopolysaccharide (LPS) to construct the cell inflammatory injury model. Subsequently, the expression of IGFBP7 was detected by qPCR and western blot. Next, IGFBP7 interference plasmid was constructed, and cell viability and apoptosis were detected by CCK8, flow cytometry and western blot. ELISA and other techniques were used to detect the inflammatory level. Autophagy and mitochondrial activities were detected by immunofluorescence and other techniques, and mitophagy-related proteins were detected by western blot. To further investigate the regulatory mechanism of IGFBP7, we administered cyclosporin A, a mitophagy inhibitor, and then detected apoptosis and inflammation. The expression of IGFBP7 was significantly increased in LPS-induced WI-38 cells. Interference with IGFBP7 expression in LPS-induced cells significantly increased cell activity, decreased apoptosis and cellular inflammation levels. During this process, mitophagy was enhanced. Further addition of cyclosporin A significantly reversed the protective effect of IGFBP7 knockdown. To be concluded, inhibition of IGFBP7 alleviates LPS-induced inflammation and apoptosis in WI-38 cells via enhancing mitophagy.