Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (7): 10-18.doi: 10.6040/j.issn.1671-7554.0.2021.0335

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Effects of calcitriol on EMT induced by TGF-β1 in asthma

ZHANG Qian, QIN Mingming, HE Xuejia, CAI Qiujing, ZHANG Yamin, LI Qingsu, ZHU Weiwei   

  1. Department of Pediatrics, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250013, Shandong, China
  • Published:2021-07-16

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Abstract: Objective To investigate the effects of calcitriol on the epithelial-mesenchymal transformation(EMT)of human bronchial epithelial cells(BEAS-2B)induced by transforming growth factor-β1(TGF-β1), and to provide reference for the prevention and treatment of asthma airway remodeling. Methods The optimal time of TGF-β1 acting on BEAS-2B cells to induce EMT was screened, and the cells were divided into blank group, 24 h TGF-β1 group, 48h TGF-β1 group, and 72 h TGF-β1 group. The optimal concentration of TGF-β1 acting on BEAS-2B cells to induce EMT was screened, and the cells were divided into blank group, 0.1 ng/mL TGF-β1 group, 1 ng/mL TGF-β1 group, 10 ng/mL TGF-β1 group, and 100 ng/mL TGF-β1 group. After pretreatment with calcitriol, the cells were divided into blank group, TGF-β1 group, calcitriol group, and TGF-β1+calcitriol group. The expressions of E-Cadherin, N-Cadherin, p-Akt and p-mTOR were detected with Western blotting. The migration ability of cells was detected with Transwell assay and scratch test. Results Western blotting showed statistically significant differences in the expressions of E-Cadherin(F=53.245, P<0.001)and N-Cadherin(F=54.429, P<0.001)in the blank group, 24 h TGF-β1 group, 48 h TGF-β1 group and 72 h TGF-β1 group. The expression of E-Cadherin in the 1ng/mL TGF-β1 group, 10 ng/mL TGF-β1 group and 100 ng/mL TGF-β1 group were significantly different with that in the blank group(F=27.368, P<0.001), and the expression of N-Cadherin was also different(F=14.272, P<0.001), among which the 10ng/ml TGF-β1 group for 48h showed the most significant difference. TGF-β1 induced the expression of PI3K/Akt signaling pathway related proteins and the expressions of interstitial markers in human bronchial epithelial cells, and the effects of TGF-β1 were statistically significant(P<0.001). However, calcitriol attenuated the effects, and the effects of calcitriol were statistically significant(P<0.001). There was no interaction between TGF-β1 and calcitriol(P>0.05). The results of Transwell test and scratch test showed that the migration ability of BEAS-2B cells in TGF-β1 treatment group was increased compared with that in the blank group(P<0.001). Compared with the TGF-β1 group, the TGF-β1+calcitriol group had decreased migration ability(P<0.001). Conclusion Calcitriol can inhibit the EMT bronchial epithelial cells induced by TGF-β1, thereby reducing airway inflammation and airway remodeling in asthma, which may involve calcitriol reducing the TGF-β1-activated proteins of PI3K/Akt/mTOR signaling pathway.

Key words: Calcitriol, Transforming growth factor-β1, Epithelial-mesenchymal transition, PI3K/Akt/mTOR pathway, Asthma

CLC Number: 

  • R725
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