ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO957

JNK-Associated Leucine Zipper Protein (Jlp) Protects Against Renal Fibrosis by Counteracting TGF-Beta1-Induced Profibrotic Effects and Autophagy on Renal Tubular Epithelial Cells

Session Information

Category: Pathology and Lab Medicine

  • 1601 Pathology and Lab Medicine: Basic

Author

  • Wang, Huiming, Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
Background

Renal fibrosis is a process involving a wide range of cells and molecules and is controlled by both profibrotic and antifibrotic forces. TGF-β1 has been identified as the primary driver of renal fibrosis, but direct targeting TGF-β1 in clinical trials has yielded no promising therapeutic effects. In this study, we identified the JNK-associated leucine zipper protein (Jlp) as a novel endogenous antifibrotic factor.

Methods

We studied the role of JLP in regulating the progress of renal fibrosis in vivo using the UUO mice model with jlp wildtype, jlp deficient, as well as jlp overexpression genotype, and explore the molecular mechanism in vitro on the tubular epithelial cells.

Results

We found that Jlp was predominantly expressed in renal tubular epithelial cells (TECs) in human or mouse kidneys in normal conditions, whereas Jlp was downregulated in fibrotic kidneys, including in kidneys of unilateral ureteral obstruction (UUO) mouse model and in kidneys of advanced CKD patients. In UUO mouse model, global or TECs-specific deletion of Jlp resulted in more severe lesion of kidney fibrosis, whereas TECs-specific transgenic expression of Jlp brought about the beneficial effects of fibrosis resistance. The protective role of Jlp in renal fibrosis could be ascribed to its potentials of overall counteracting the profibrotic effects induced by TGF-β1 through negatively regulating TGF-β1 expression, counteracting TGF-β1 induced ECM production, epithelial-to-mesenchymal transition (EMT), apoptosis, cell cycle arrest, and autophagy in TECs. The protective effects of Jlp could be compromised by its downregulation mediated by TGF-β1 and FGF-2 but not the inflammatory factor TNFα, implying that kidney fibrosis is a consequence of unbalanced forces of profibrotic factor TGF-β1 and FGF-2 and antifibrotic factor Jlp.

Conclusion

JLP is a novel endogenous antifibrotic molecule in renal fibrosis.