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
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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.