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
Affiliations
Maoqing Tian
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Lu Zhang
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Meng Zhang
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Liwen Qiao
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Bingqing Xu
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Chen Li
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Shan Liu
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China; Department of Nephrology, Minda Hospital, Affiliated with Hubei University for Nationalities, Enshi, China
Yuan Song
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Zhongping Wei
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Yujuan Wang
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Huiming Wang
Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China; Corresponding author
Summary: 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.
