The role and mechanism of 1,25-dihydroxyvitamin D3 in regulating the Rho-kinase signaling pathway in asthmatic rats

Wei-Min Tian; Wei-Wei Chen; Yu Chen; Chen-Xi Lin; Jin-Xian Huang; Ya-Ping Song; Yun-Gang Yang

doi:10.21037/tp-20-365

The role and mechanism of 1,25-dihydroxyvitamin D₃ in regulating the Rho-kinase signaling pathway in asthmatic rats

Transl Pediatr. 2021 Apr;10(4):773-782. doi: 10.21037/tp-20-365.

Authors

Wei-Min Tian¹, Wei-Wei Chen², Yu Chen³, Chen-Xi Lin³, Jin-Xian Huang¹, Ya-Ping Song⁴, Yun-Gang Yang⁵

Affiliations

¹ Department of Pediatrics, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
² Department of Pediatrics, Affiliated Hospital of Jining Medical University, Jining, China.
³ Department of Pediatrics, Zhongshan Hospital of Xiamen University, Xiamen, China.
⁴ School of Medicine, Xiamen University, Xiamen, China.
⁵ Department of Pediatrics, The First Affiliated Hospital of Xiamen University, Xiamen, China.

Abstract

Background: Bronchial asthma (referred to as asthma in the present study) is the most common chronic airway inflammatory disease in childhood. The present study aimed to investigate the effect of 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃] on VDR expression, which is closely associated with asthmatic airway smooth muscle cells (ASMCs), and explored its role and mechanism in the Rho-kinase signaling pathway.

Methods: The acute asthma model was induced by ovalbumin (OVA) and pertussis bacillus, and ASMCs obtained from asthmatic rats were cultured in vitro. These cells were randomly divided into five groups: control (N) group, TNF-α (TNF) group, 1,25-(OH)₂D₃ (VD) group, dexamethasone (DXM) group, and 1,25-(OH)₂D₃ + DXM (L) group. The protein expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by western blot, and the mRNA expression levels of VDR, ROCK, MLC20 and P-MLC20 were detected by real-time quantitative PCR.

Results: The expression of ROCK, MLC20 and P-MLC20 in each treatment group were significantly lower, when compared to the TNF group (P<0.05), but this remained stronger than (P<0.05) or similar to (P>0.05) that in the N group.

Conclusions: The regulation mechanism of 1,25-(OH)₂D₃ in alleviating asthma should be correlated to its regulation of the expression of related signaling molecules in the Rho-kinase signaling pathway, and this effect may be achieved by regulating the mRNA and protein expression of the VDR gene.

Keywords: 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]; Asthma; IL-8; Rho; VDR; eotaxin.