Nephroblastoma Overexpressed Protein (NOV/CCN3) Elevated Expression of Inflammation Regulators in a Model of Sepsis-Induced Lung Injury.

Abstract

Nephroblastoma overexpressed protein (NOV, also named CCN3), a member of the CCN (Cy61, CTGF, and NOV) family, is a critical biological marker of the severity of acute respiratory distress syndrome (ARDS). However, no evidence has been presented that CCN3 directly affects acute lung injury (ALI) or ARDS. Intratracheal infusion of LPS is an established method to simulate sepsis and induce ALI. To examine the effect of CCN3 on ALI, we developed in vivo and in vitro models of this disease on mice and type II alveolar epithelial A549 cells, respectively. To further clarify the role of CCN3 in ALI, we constructed a CCN3 overexpression model based on plasmid transfection. The results showed that CCN3 expression was up-regulated in LPS-induced ALI both in vivo and in vitro; this effect was time- and dose-dependent. ELISA revealed that overexpression of CCN3 increased the levels of proinflammatory cytokines IL-1β and TNFα. Flow cytometry and Western blotting showed that overexpression of CCN3 increased the expression of proapoptotic protein Bax and decreased the expression of anti-apoptotic protein Bcl-2, thereby promoting apoptosis of A549 cells. The results suggest that CCN3 antagonists can inhibit progression of inflammation and the development of apoptosis in lung epithelial cells, thereby exerting a possible therapeutic effect in ALI.