Small nucleolar RNA host gene 3 regulates sepsis-induced acute lung injury and inflammation by targeting microRNA-186-5p.

In the process of sepsis-induced acute lung injury (ALI), reducing the inflammatory response is crucial for restoring cellular and barrier function. The expression of small nucleolar RNA host gene 3 (SNHG3) is increased in the serum of sepsis patients, yet whether SNHG3 is involved in regulating the pathophysiology of ALI remains unclear. This study aims to investigate the effect of SNHG3 on sepsis-induced acute lung injury and explore its underlying mechanism. Sepsis-induced ALI models were established using lipopolysaccharide (LPS)-treated mice and lung endothelial cells. SNHG3 expression was inhibited, and ALI was evaluated by assessing lung pathological changes, levels of inflammatory factors, cell apoptosis, and expression levels of tight junction proteins. Public databases were used to predict the downstream targets of SNHG3, and further in vitro studies were conducted to clarify the role and mechanism of SNHG3. The results indicated that SNHG3 was upregulated in LPS-treated mice. SNHG3 inhibition alleviated lung inflammation, reduced IL-1β and IL-6, increased claudin-5 and zonula occludens-1 (ZO-1), and decreased apoptosis. SNHG3 targeted miR-186-5p. Downregulation of miR-186-5p activated the Wnt/β-catenin signaling pathway. SNHG3 overexpression inhibited miR-186-5p, activated the Wnt/β-catenin pathway, and exacerbated the inflammatory response and barrier damage of microvascular endothelial cells. In conclusion, SNHG3 activates the Wnt/β-catenin pathway by targeting and inhibiting miR-186-5p, thereby exacerbating inflammation and apoptosis in sepsis-induced ALI.