JLP/Foxk1/N-cadherin axis fosters a partial epithelial-mesenchymal transition state in epithelial tubular cells

Maoqing Tian; Lu Zhang; Meng Zhang; Liwen Qiao; Bingqing Xu; Chen Li; Shan Liu; Yuan Song; Zhongping Wei; Yujuan Wang; Huiming Wang

doi:10.1016/j.isci.2023.106396

JLP/Foxk1/N-cadherin axis fosters a partial epithelial-mesenchymal transition state in epithelial tubular cells

iScience. 2023 Mar 14;26(4):106396. doi: 10.1016/j.isci.2023.106396. eCollection 2023 Apr 21.

Authors

Maoqing Tian¹, Lu Zhang¹, Meng Zhang¹, Liwen Qiao¹, Bingqing Xu¹, Chen Li¹, Shan Liu^{1

2}, Yuan Song¹, Zhongping Wei¹, Yujuan Wang¹, Huiming Wang¹

Affiliations

¹ Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
² Department of Nephrology, Minda Hospital, Affiliated with Hubei University for Nationalities, Enshi, China.

Abstract

Renal tubular epithelial cells (TECs) undergoing partial epithelial-mesenchymal transition (pEMT) during renal fibrosis has been recognized as a featuring and detrimental event. However, the mechanism for redirecting the cell fate of pEMT remains unclear. Here we mapped the temporal expression trajectories of a series of EMT-related molecules in renal fibrosis. It revealed a unique expression profile of N-cadherin of initial rising and late dropdown, which is distinct from that of other mesenchymal markers. The transcription factor Foxk1, which serves as a negative regulator of the N-cadherin gene, was induced by TGF-β1 but was tightly regulated in the presence of JNK-associated leucine zipper protein (JLP). The loss of JLP resulted in Foxk1 induction, leading to N-cadherin downregulation and compromised cell viability. We propose a novel axis consisting of JLP/Foxk1/N-cadherin in shaping the EMT program and suggest JLP as the checkpoint of the EMT continuum during renal fibrosis progression.

Keywords: Biological sciences; Health sciences; Molecular biology; Molecular mechanism of gene regulation; Molecular medicine.