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Lookup NU author(s): Dr Henrique De Paula LemosORCiD, Dr Lei Huang
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
© The Author(s) 2026. Background: Renal fibrosis is the common outcome of chronic renal disease. Currently, there are no effective therapies. Fibroblast activation and extracellular matrix accumulation are key processes driving renal fibrosis. Methods and results: Fibroblast activation protein (FAP) is highly induced in injured kidneys, and immunofluorescence staining revealed that FAP is mainly expressed in Platelet-derived growth factor receptor-beta (PDGFRβ)+ and alpha-smooth muscle actin (α-SMA)+ myofibroblasts in kidney samples from mice with renal fibrosis and patients with chronic kidney diseases or post-acute kidney injury. In this study, targeting FAP as a strategy for treating renal fibrosis is tested using two preclinical animal models: the mouse models of unilateral ureteral obstruction and unilateral renal ischemia–reperfusion. Adoptive transfer of T cells expressing chimeric antigen receptor specific to FAP or administration of an FAP inhibitor (SP-13786) significantly alleviated kidney fibrosis in both mouse models. Eliminating FAP+ fibroblasts using chimeric antigen receptor T-cell (CAR-T) therapy or inhibiting the FAP prevented fibroblast overactivation, proliferation, and migration, promoted apoptosis, and effectively suppressed other myofibroblast populations. Conclusions: Overall, we report herein that targeting FAP offers a novel promising treatment approach for renal fibrosis.
Author(s): Gong L, Lu X, Ma N, Lu T, Gong Y, Hao L, Xu W, Zhang Q, Chen X, Mo Q, Tan J, de Paula Lemos H, Speechley A, Tu W, Cai J, Huang L, Zhu W, Wu S
Publication type: Article
Publication status: Published
Journal: Cellular and Molecular Biology Letters
Year: 2026
Volume: 31
Online publication date: 29/03/2026
Acceptance date: 24/02/2026
Date deposited: 19/05/2026
ISSN (print): 1425-8153
ISSN (electronic): 1689-1392
Publisher: BioMed Central Ltd
URL: https://doi.org/10.1186/s11658-026-00898-9
DOI: 10.1186/s11658-026-00898-9
Data Access Statement: Data, analytic methods, and study materials will be made available to other researchers on request. The RNA-sequencing data that support the findings of this study have been deposited in the Genome Sequence Archive in National Genomics Data Center, China National Center for Bioinformation/Beijing Institute of Genomics, Chinese Academy of Sciences (accession no. CRA016872) that are publicly accessible at https://ngdc.cncb.ac.cn/gsa. The single-cell mRNA-seq data are publicly accessible at http://humphreyslab.com/SingleCell.
PubMed id: 41906119
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