Sinomenine Relieves Airway Remodeling By Inhibiting Epithelial-Mesenchymal Transition Through Downregulating TGF-β1 and Smad3 Expression In Vitro and In Vivo

Abstract

Airway remodeling is associated with dysregulation of epithelial-mesenchymal transition (EMT) in patients with asthma. Sinomenine (Sin) is an effective, biologically active alkaloid that has been reported to suppress airway remodeling in mice with asthma. However, the molecular mechanisms behind this effect remain unclear. We aimed to explore the potential relationship between Sin and EMT in respiratory epithelial cells in vitro and in vivo. First, 16HBE cells were exposed to 100 μg/mL LPS and treated with 200 μg/mL Sin. Cell proliferation, migration, and wound healing assays were performed to evaluate EMT, and EMT-related markers were detected using Western blotting. Mice with OVA-induced asthma were administered 35 mg/kg or 75 mg/kg Sin. Airway inflammation and remodeling detection experiments were performed, and EMT-related factors and proteins in the TGF-β1 pathway were detected using IHC and Western blotting. We found that Sin suppressed cell migration but not proliferation in LPS-exposed 16HBE cells. Sin also inhibited MMP7, MMP9, and vimentin expression in 16HBE cells and respiratory epithelial cells from mice with asthma. Furthermore, it decreased OVA-specific IgE and IL-4 levels in serum, relieved airway remodeling, attenuated subepithelial collagen deposition, and downregulating TGF-β1and Smad3 expression in mice with asthma. Our results suggest that Sin suppresses EMT by inhibiting IL-4 and downregulating TGF-β1 and Smad3 expression.

Sinomenine accelerate wound healing in rats by augmentation of antioxidant, anti-inflammatory, immunuhistochemical pathways

“…On the other side, SN-treated rats showed significantly increased HXP levels in their cured wound tissue, indicating higher collagen content that might be correlated with its higher wound closure percentages. Our results were following previous results, which showed SN efficacy in positive regulation of subepithelial collagen deposition, and other tissue proteins that helped in relieving Airway remodeling in mice with asthma [ 62 ]. Similar effects of SN on the positive regulation of hydroxyproline and collagen proteins have been found in a nanofiber study for wound healing [ 63 ].…”

Bioactivities and Mechanisms of Action of Sinomenine and Its Derivatives: A Comprehensive Review

“…He et al reported that SIN (607.2 mM) impeded 16HBe cell migration and suppressed the expression of MMP-7/-9 and vimentin. Additionally, SIN (35 and 75 mg/kg) reduced serum levels of specific IgE and IL-4 in ovalbumin-induced asthmatic mice, mitigated airway remodeling, lessened subepithelial collagen deposition, and inhibited EMT by downregulating TGF-B1 and Smad3 [ 211 ]. J.L.…”

Exosomal Non-Coding RNAs: Novel Regulators of Macrophage-Linked Intercellular Communication in Lung Cancer and Inflammatory Lung Diseases

“…SC-induced M2 macrophage exosomes carrying miR-30b-5p reduce airway epithelial cell pyroptosis via restricting IRF7, resulting in restraining asthma progression [ 138 ]. EMT can be triggered by the TGF-β1/Smad3 signaling pathway and can support airway remodeling in asthma [ 139 ]. miR-21-5p is highly expressed in lung tissues of mice with ovalbumin (OVA)-induced asthma.…”