British journal of pharmacology · 2026
Honokiol regulates Acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis via the miR-19a-3p/POSTN axis.
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Liu Weilun, Wang Hsiaohsuan, Kuo Hsuanfu, Yen Chiahung, Hua Modasang, Chang Chiayuan, Xu Zhiwei, Liu Ifan, Hsieh Chongchao, Hsu Chihhsin, Li Chiayang, Wang Shuchi, Chen Yunghsiang, Cheng Menghsuan, Liu Polen
Аннотация
BACKGROUND AND PURPOSE: Acute respiratory distress syndrome (ARDS) and subsequent pulmonary fibrosis are associated with high mortality and limited treatment options. Periostin (POSTN) is a profibrotic mediator predicted to be regulated by microRNA-19a-3p (miR-19a-3p), but the relevance of this axis in ARDS-associated pulmonary fibrosis remains unclear. Honokiol (HKL), a phytochemical derived from Magnolia officinalis, possesses antioxidant and anti-inflammatory properties. This study investigated whether HKL modulates the miR-19a-3p/POSTN axis in ARDS-associated lung injury and fibrosis.
EXPERIMENTAL APPROACH: Serum POSTN and miR-19a-3p levels were measured in patients with ARDS and correlated with severity. Mechanistic studies were performed using a lipopolysaccharide (LPS)-induced lung injury mouse model and macrophage-epithelial and macrophage-fibroblast co-culture systems.
KEY RESULTS: Patients with ARDS exhibited elevated serum POSTN and reduced miR-19a-3p, which were inversely correlated and associated with indices of disease severity. HKL attenuated LPS-induced lung injury and fibrotic responses, accompanied by reduced POSTN expression and preserved miR-19a-3p levels. Dual-luciferase reporter assays supported a regulatory interaction between miR-19a-3p and POSTN. HKL was associated with alterations in macrophage phenotype and reduced macrophage-associated POSTN expression. In co-culture systems, manipulation of miR-19a-3p in macrophages modulated epithelial apoptotic signalling and fibroblast activation. In vitro loss-of-function experiments suggested that miR-19a-3p contributes, at least in part, to HKL-associated protective effects.
CONCLUSION AND IMPLICATIONS: The miR-19a-3p/POSTN axis may represent a regulatory pathway associated with ARDS-related lung injury and fibrosis. HKL attenuated experimental injury and fibrotic responses in association with this axis. These findings support further pharmacological investigation of HKL in ARDS-associated lung injury and fibrosis.
EXPERIMENTAL APPROACH: Serum POSTN and miR-19a-3p levels were measured in patients with ARDS and correlated with severity. Mechanistic studies were performed using a lipopolysaccharide (LPS)-induced lung injury mouse model and macrophage-epithelial and macrophage-fibroblast co-culture systems.
KEY RESULTS: Patients with ARDS exhibited elevated serum POSTN and reduced miR-19a-3p, which were inversely correlated and associated with indices of disease severity. HKL attenuated LPS-induced lung injury and fibrotic responses, accompanied by reduced POSTN expression and preserved miR-19a-3p levels. Dual-luciferase reporter assays supported a regulatory interaction between miR-19a-3p and POSTN. HKL was associated with alterations in macrophage phenotype and reduced macrophage-associated POSTN expression. In co-culture systems, manipulation of miR-19a-3p in macrophages modulated epithelial apoptotic signalling and fibroblast activation. In vitro loss-of-function experiments suggested that miR-19a-3p contributes, at least in part, to HKL-associated protective effects.
CONCLUSION AND IMPLICATIONS: The miR-19a-3p/POSTN axis may represent a regulatory pathway associated with ARDS-related lung injury and fibrosis. HKL attenuated experimental injury and fibrotic responses in association with this axis. These findings support further pharmacological investigation of HKL in ARDS-associated lung injury and fibrosis.