JLP/Foxk1/N-cadherin axis fosters a partial epithelial-mesenchymal transition state in epithelial tubular cells
iScience(2023)
Abstract
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.
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Key words
Health sciences,Biological sciences,Molecular biology,Molecular medicine,Molecular mechanism of gene regulation
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