Research Paper Volume 12, Issue 24 pp 25469—25486
Tumor necrosis factor superfamily 14 is critical for the development of renal fibrosis
- 1 Department of Nephrology, The First Affiliated Hospital of Army Medical University (Third Military Medical University), Shapingba 400038, Chongqing, China
- 2 Department of Immunology, Basic Medicine College of Army Medical University (Third Military Medical University), Shapingba 400038, Chongqing, China
- 3 Urinary Nephropathy Center, The Second Affiliated Hospital of Chongqing Medical University, Nanan 400065, Chongqing, China
Received: November 21, 2019 Accepted: August 29, 2020 Published: November 24, 2020https://doi.org/10.18632/aging.104151
How to Cite
Copyright: © 2020 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Objective: Tumor necrosis factor superfamily protein 14 (TNFSF14) was recently identified as a risk factor in some fibrosis diseases. However, the role of TNFSF14 in renal fibrosis pathogenesis remains unknown.
Results: It was found that TNFSF14 levels were significantly increased both in UUO-induced renal fibrotic mice and in patients with fibrotic nephropathy, compared with those in controls. Accordingly, Tnfsf14 deficiency led to a marked reduction in renal fibrosis lesions and inflammatory cytokines expression in the UUO mice. Furthermore, the levels of Sphk1, a critical molecule that causes fibrotic nephropathy, were remarkably reduced in Tnfsf14 KO mice with UUO surgery. In vitro recombinant TNFSF14 administration markedly up-regulated the expression of Sphk1 of primary mouse renal tubular epithelial cells (mTECs).
Conclusion: TNFSF14 is a novel pro-fibrotic factor of renal fibrosis, for which TNFSF14 up-regulates Sphk1 expression, which may be the underlying mechanism of TNFSF14-mediated renal fibrosis.
Methods: We investigated the effect of TNFSF14 on renal fibrosis and the relationship between TNFSF14 and pro-fibrotic factor sphingosine kinase 1 (Sphk1) by using the unilateral urethral obstruction (UUO)-induced mice renal fibrosis as a model and the specimen of patients with fibrosis nephropathy, by Masson trichrome staining, immunohistochemistry, qRT-PCR, and western blot analysis.