Ziyu  Zhang; Zepeng  Li; Xiao  Chen; Yinhua  Wang; Xianwei Li

doi:10.14715/cmb/2023.69.5.24

Issue

Vol. 69 No. 5: Issue 5

Issue Published : August 9, 2023

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Effect of AR gene-specific knockout on the process of radiation-induced pulmonary fibrosis and its mechanism

AR gene-specific knockout in RIPF

https://doi.org/10.14715/cmb/2023.69.5.24

Ziyu Zhang

Anhui Medical University, The First Clinical Medical College, Hefei 230032, China

Zepeng Li

Department of Pharmacology, Wannan Medical College, Wuhu 241002, China

Xiao Chen

Department of Pharmacology, Wannan Medical College, Wuhu 241002, China

Yinhua Wang

Department of Oncology, Wuhu Second People's Hospital Affiliated to East China University of Science and Technology, Wuhu 241000, China

Xianwei Li

Department of Pharmacology, Wannan Medical College, Wuhu 241002, China

Corresponding Author(s) : Xianwei Li

xianwei_li@publisher.org.cn

Cellular and Molecular Biology, Vol. 69 No. 5: Issue 5
Article Published : May 31, 2023

Abstract

Numerous studies have proved that epithelial-mesenchymal transition (EMT) of lung epithelial cells is one of the important causes of radiation-induced pulmonary fibrosis (RIPF). Aldose reductase (AR) is a monomer enzyme in the polyglycolic metabolic pathway and belongs to the aldo-keno reductase protein superfamily. Our previous studies have found that AR as one of the most significantly up-regulated genes was associated with the development of bleomycin-induced PF in rats. It is not clear whether aldose reductase is related to the regulation of radiation-induced EMT and mediates RIPF. AR-knockout mice, wild-type mice and lung epithelial cells were induced by radiation to establish a RIPF animal model and EMT system, to explore whether AR is mediation to RIPF through the EMT pathway. In vivo, AR deficiency significantly alleviated radiation-induced histopathological changes, reduced collagen deposition and inhibited collagen I, matrix metalloproteinase 2 (MMP2) and Twist1 expression. In addition, AR knockout up-regulated E-cadherin expression and up-regulated α-SMA and Vimentin expression. In vitro, AR, collagen I and MMP2 expression were increased in lung epithelial cells after radiation, which was accompanied by Twist1 expression up-regulation and EMT changes evidenced by decreased E-cadherin expression and increased α-SMA and Vimentin expression. Knockdown or inhibition of AR inhibited the expressions of Twist1, MMP2 and collagen I, and reduced cell migration and reversed radiation-induced EMT. These results indicated that aldose reductase may be related to radiation-induced lung epithelial cells EMT, and that inhibition of aldose reductase might be a promising treatment for RIPF.

Keywords

aldose reductase EMT RIPF Twist1

Zhang, Z. ., Li, Z. ., Chen, X. ., Wang, Y. ., & Li, X. (2023). Effect of AR gene-specific knockout on the process of radiation-induced pulmonary fibrosis and its mechanism: AR gene-specific knockout in RIPF . Cellular and Molecular Biology, 69(5), 156–162. https://doi.org/10.14715/cmb/2023.69.5.24