Zinc salicylate reduces airway smooth muscle cells remodelling by blocking mTOR and activating p21(Waf1/Cip1).

Asthma is characterized by chronic inflammation and tissue remodeling of the airways. Remodeling is resistant to pharmaceutical therapies. This study investigated the effect of zinc salicylate-methylsulfonylmethane (Zn-Sal-MSM) compared to zinc salicylate (Zn-Sal), or sodium salicylate (Na-Sal), or zinc chloride (ZnCl2) on remodeling parameters of human airway smooth muscle cells (ASMC). Human ASMC obtained from asthma patients (n=7) and non-asthma controls (n=7) were treated with one of the reagents. Cell proliferation and viability was determined by direct cell counts and MTT assay. The expression of and phosphorylation proteins was determined by Western-blotting, ELISA, immunofluorescence, and mass spectrometry. Extracellular matrix deposition by ELISA. Zn-Sal-MSM, Zn-Sal and Na-Sal (0.1-100 µg/mL) significantly reduced PDGF-BB-induced proliferation in a concentration dependent manner, while ZnCl2 was toxic. The reduced proliferation correlated with increased expression of the cell cycle inhibitor p21(Waf1/Cip1), and reduced activity of Akt, p70S6K, and Erk1/2. Zn-Sal-MSM, Zn-Sal, but not Na-Sal reduced the deposition of fibronectin and collagen type-I. Furthermore, Zn-Sal-MSM reduced the mitochondria specific COX4 expression. Mass spectrometry indicated that Zn-Sal-MSM modified the expression of several signaling proteins and zinc-dependent enzymes. In conclusion, Zn-Sal-MSM and Zn-Sal potentially prevent airway wall remodeling in asthma by inhibition of both the Erk1/2 and mTOR signaling pathways. Copyright © 2020. Published by Elsevier Inc.

Citation

Lei Fang, Michael Roth, Chong Teck S'ng, Michael Tamm, Bo Han, Ba Xuan Hoang. Zinc salicylate reduces airway smooth muscle cells remodelling by blocking mTOR and activating p21(Waf1/Cip1). The Journal of nutritional biochemistry. 2021 Mar;89:108563

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PMID: 33326841

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