Zhu H, Liu L, Yang M, Zhu X, Cai J, Huang H
Department of Intensive Care Unit, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Bull Exp Biol Med. 2025 Feb;178(4):453-459. doi: 10.1007/s10517-025-06355-5. Epub 2025 Mar 29.
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.
肾母细胞瘤过表达蛋白（NOV，也称为CCN3）是CCN（Cy61、CTGF和NOV）家族的成员，是急性呼吸窘迫综合征（ARDS）严重程度的关键生物学标志物。然而，尚无证据表明CCN3直接影响急性肺损伤（ALI）或ARDS。气管内注入脂多糖是模拟脓毒症并诱导ALI的一种既定方法。为了研究CCN3对ALI的影响，我们分别在小鼠和II型肺泡上皮A549细胞上建立了该疾病的体内和体外模型。为了进一步阐明CCN3在ALI中的作用，我们基于质粒转染构建了CCN3过表达模型。结果表明，在体内和体外，LPS诱导的ALI中CCN3表达均上调；这种作用具有时间和剂量依赖性。酶联免疫吸附测定显示，CCN3过表达增加了促炎细胞因子IL-1β和TNFα的水平。流式细胞术和蛋白质印迹法显示，CCN3过表达增加了促凋亡蛋白Bax的表达，降低了抗凋亡蛋白Bcl-2的表达，从而促进了A549细胞的凋亡。结果表明，CCN3拮抗剂可以抑制肺上皮细胞炎症进展和凋亡发生，从而在ALI中发挥可能的治疗作用。
