Pericyte-mediated intercellular crosstalk in renal fibrosis: regulatory mechanisms and intervention strategies
4 affiliations
- 1Department of Chinese Medicine, Jiangsu College of Nursing, Huaian, China
- 2Department of Clinical Medicine, Jiangsu College of Nursing, Huaian, China
- 3Department of Gerontology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, China
- 4Jiangsu Province Engineering Research Center of Precise Prevention in the Digestive and Reproductive System Cancers, Jiangsu College of Nursing, Huaian, China
Abstract
Chronic kidney disease continues to increase in global prevalence, with renal fibrosis serving as a major pathological driver of end-stage renal disease and imposing a substantial burden on global public health. Renal pericytes, essential mesenchymal cells distributed along capillary walls, have been redefined from mere structural vascular support cells to multidirectional communication hubs that coordinate homeostasis of the renal microenvironment. Under persistent injurious stimuli, pericytes detach from capillary walls, migrate, and become activated, undergoing pericyte-to-myofibroblast transition and emerging as a predominant source of renal interstitial myofibroblasts. This process promotes capillary rarefaction and aberrant extracellular matrix deposition, thereby establishing a vicious cycle of “vascular loss–exacerbated hypoxia–progressive fibrosis”. Herein, the pericyte-mediated cellular interactome and its molecular regulatory mechanisms in renal fibrosis are systematically reviewed, with particular emphasis on the bidirectional communication of pericytes with vascular endothelial cells, renal tubular epithelial cells, immune cells (including macrophages, T lymphocytes, neutrophils, and mast cells), and fibroblasts; direct renal evidence for these interactions is explicitly distinguished from indirect or hypothetical mechanisms inferred from non-renal models. The roles of key signaling pathways, including Ang/Tie2, PDGF/PDGFRβ, TGF-β/Smad, Hippo-YAP/TAZ, Wnt/β-catenin, and Notch, in regulating these interactions are further elucidated, with clarification of the extent to which each pathway is pericyte-intrinsic or involves pericytes as one of several effector cell types. Additionally, recent advances in intervention strategies targeting pericyte-mediated crosstalk are critically appraised according to the directness of pericyte targeting and the strength of the supporting evidence, encompassing mesenchymal stem cell therapy, engineered extracellular vesicles, nanomedicine-based drug delivery systems, and natural pharmaceutical therapies. Current evidence remains constrained by the lack of pericyte-specific markers, the reliance on rodent models, and the predominantly preclinical stage of available interventions; nevertheless, a comprehensive understanding of the pericyte-mediated cellular interactome may provide an important theoretical foundation and candidate therapeutic targets for the prevention and treatment of renal fibrosis.
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BibTeX
@article{tang2026pericytemediated,
title = {{Pericyte-mediated intercellular crosstalk in renal fibrosis: regulatory mechanisms and intervention strategies}},
author = {Lei Tang and Wei Qiao and Suyu Wang and Zhao Wang and Shaohong Zhang and Ling Liu and Wenbo Zhu},
journal = {Frontiers in Physiology},
year = {2026},
month = oct,
doi = {10.3389/fphys.2026.1963705},
url = {https://doi.org/10.3389/fphys.2026.1963705},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Pericyte-mediated intercellular crosstalk in renal fibrosis: regulatory mechanisms and intervention strategies
AU - Lei Tang
AU - Wei Qiao
AU - Suyu Wang
AU - Zhao Wang
AU - Shaohong Zhang
AU - Ling Liu
AU - Wenbo Zhu
PY - 2026
DA - 2026/10/21
JO - Frontiers in Physiology
DO - 10.3389/fphys.2026.1963705
UR - https://doi.org/10.3389/fphys.2026.1963705
AB - Chronic kidney disease continues to increase in global prevalence, with renal fibrosis serving as a major pathological driver of end-stage renal disease and imposing a substantial burden on global public health. Renal pericytes, essential mesenchymal cells distributed along capillary walls, have been redefined from mere structural vascular support cells to multidirectional communication hubs that coordinate homeostasis of the renal microenvironment. Under persistent injurious stimuli, pericytes detach from capillary walls, migrate, and become activated, undergoing pericyte-to-myofibroblast transition and emerging as a predominant source of renal interstitial myofibroblasts. This process promotes capillary rarefaction and aberrant extracellular matrix deposition, thereby establishing a vicious cycle of “vascular loss–exacerbated hypoxia–progressive fibrosis”. Herein, the pericyte-mediated cellular interactome and its molecular regulatory mechanisms in renal fibrosis are systematically reviewed, with particular emphasis on the bidirectional communication of pericytes with vascular endothelial cells, renal tubular epithelial cells, immune cells (including macrophages, T lymphocytes, neutrophils, and mast cells), and fibroblasts; direct renal evidence for these interactions is explicitly distinguished from indirect or hypothetical mechanisms inferred from non-renal models. The roles of key signaling pathways, including Ang/Tie2, PDGF/PDGFRβ, TGF-β/Smad, Hippo-YAP/TAZ, Wnt/β-catenin, and Notch, in regulating these interactions are further elucidated, with clarification of the extent to which each pathway is pericyte-intrinsic or involves pericytes as one of several effector cell types. Additionally, recent advances in intervention strategies targeting pericyte-mediated crosstalk are critically appraised according to the directness of pericyte targeting and the strength of the supporting evidence, encompassing mesenchymal stem cell therapy, engineered extracellular vesicles, nanomedicine-based drug delivery systems, and natural pharmaceutical therapies. Current evidence remains constrained by the lack of pericyte-specific markers, the reliance on rodent models, and the predominantly preclinical stage of available interventions; nevertheless, a comprehensive understanding of the pericyte-mediated cellular interactome may provide an important theoretical foundation and candidate therapeutic targets for the prevention and treatment of renal fibrosis.
SN - 1664-042X
ER -