lignans and Airway-Remodeling

Asthma is a chronic inflammatory disorder of the airways. Schisandrin B (SB) is the main effective component. This study investigated the effects of SB on airway inflammation and airway remodeling in asthma. The rat model of asthma was established. The rats were treated with SB to evaluate the effects of SB on airway inflammation, airway remodeling, NLRP3 inflammasome activation, and pyroptosis. Alveolar macrophages of rats were isolated, and the macrophage inflammatory model was established by lipopolysaccharide (LPS) induction. The LPS-induced macrophages were treated with SB. The binding relationship between miR-135a-5p and TPRC1 was analyzed. LPS + SB-treated macrophages were transfected with miR-135a-5p inhibitor. The expressions of key factors of the STAT3/NF-κB pathway were detected. SB reduced airway inflammation and airway remodeling in asthmatic rats. SB inhibited NLRP3 inflammasome activation and reduced pyroptosis in asthmatic rats and LPS-induced macrophages. SB reversely regulated the miR-135a-5p/TRPC1 axis. Downregulation of miR-135a-5p attenuated the inhibitory effect of SB on NLRP3 inflammasome activation. SB inhibited the STAT3/NF-κB pathway via the miR-135a-5p/TRPC1 axis. In conclusion, SB inhibited NLRP3 inflammasome activation and reduced pyroptosis via the miR-135a-5p/TRPC1/STAT3/NF-κB axis, thus alleviating airway inflammation and airway remodeling in asthma. This study may confer novel insights for the management of asthma.

Topics: Airway Remodeling; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Cells, Cultured; Cyclooctanes; Disease Models, Animal; Female; Inflammasomes; Lignans; Lung; Macrophages, Alveolar; MicroRNAs; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pneumonia; Polycyclic Compounds; Pyroptosis; Rats, Sprague-Dawley; Signal Transduction; STAT3 Transcription Factor; TRPC Cation Channels

Airway smooth muscle cell (ASMC) was known to involve in the pathophysiology of asthma. Schisandrin B was reported to have anti-asthmatic effects in a murine asthma model. However, the molecular mechanism involving in the effect of Schisandrin B on ASMCs remains poorly understood. Sprague-Dawley rats were divided into three groups: rats as the control (Group 1), sensitized rats (Group 2), sensitized rats and intragastric-administrated Schisandrin B (Group 3). The expression of miR-135a and TRPC1 was detected in the rats from three groups. Platelet-derived growth factor (PDGF)-BB was used to induce the proliferation of isolated ASMCs, and the expression of miR-135a and TRPC1 was detected in PDGF-BB-treated ASMCs. Cell viability was examined in ASMCs transfected with miR-135a inhibitor or si-TRPC1. The expression of TRPC1 was examined in A10 cells pretreated with miR-135a inhibitor or miR-135a mimic. In this study, we found that Schisandrin B attenuated the inspiratory and expiratory resistances in sensitized rats. Schisandrin B upregulated the mRNA level of miR-135a and decreased the expression of TRPC1 in sensitized rats. In addition, Schisandrin B reversed the expression of miR-135a and TRPC1 in PDGF-BB-induced ASMCs. Si-TRPC1 abrogated the increasing proliferation of ASMCs induced by miR-135a inhibitor. We also found that miR-135a regulated the expression of TRPC1 in the A10 cells. These results demonstrate that Schisandrin B inhibits the proliferation of ASMCs via miR-135a suppressing the expression of TRPC1.

Topics: Airway Remodeling; Animals; Apoptosis; Asthma; Cell Proliferation; Cell Survival; Cells, Cultured; Cyclooctanes; Lignans; Male; MicroRNAs; Myocytes, Smooth Muscle; Polycyclic Compounds; Random Allocation; Rats; Rats, Sprague-Dawley; TRPC Cation Channels; Up-Regulation