Deubiquitinase USP7 stabilizes the histone demethylase KDM5B and promotes the progression of renal fibrosis through the TSC1/mTOR axis

Lv S, Zhang Xiaoyan et al. · 2026 · Molecular biomedicine · Atlas ID LV2026S

What this study shows

USP7 deubiquitinates and stabilizes the histone demethylase KDM5B, which represses TSC1 transcription and thereby activates mTOR, promoting kidney fibrosis in two mouse injury models; USP7 is upregulated in human CKD kidneys and correlates with fibrosis severity. Genetic or pharmacological USP7 inhibition restores TSC1 expression, suppresses mTOR activation, and attenuates fibrosis in these mice, making the USP7-KDM5B-TSC1-mTOR axis a candidate intervention point; the human data are correlative only.

Abstract

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Ubiquitin-specific protease 7 (USP7) is a deubiquitinase implicated in tumor progression; its role in renal fibrosis was unclear. USP7 was significantly upregulated in kidneys of patients with chronic kidney disease (CKD), correlating with fibrotic lesions and renal dysfunction. Genetic depletion and pharmacological blockade of USP7 significantly attenuated fibroblast activation and extracellular matrix deposition in unilateral ureteral obstruction and unilateral renal ischemia-reperfusion injury mouse models.

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At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (UUO and unilateral renal ischemia-reperfusion injury models); human CKD kidney tissue (correlative)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (UUO and unilateral renal ischemia-reperfusion injury models); human CKD kidney tissue (correlative)
Journal	Molecular biomedicine
Year	2026
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1186/s43556-026-00531-3 · PMID 42554966 · Free full text (PMC13442801)

Extracted findings

Intervention	Genetic (USP7 knockdown) and pharmacological USP7 inhibition
Target	USP7 -> KDM5B -> TSC1 -> mTOR axis
Model	Mouse (UUO, unilateral renal I/R injury models); human CKD kidney tissue (correlative)
Effect	USP7 depletion/inhibition restores TSC1 expression, suppresses mTOR activation, and attenuates fibroblast activation and renal fibrosis

In the Atlas

Cite this paper

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Lv, S., et al. (2026). Deubiquitinase USP7 stabilizes the histone demethylase KDM5B and promotes the progression of renal fibrosis through the TSC1/mTOR axis. Molecular biomedicine. https://doi.org/10.1186/s43556-026-00531-3

@article{LV2026S,
  author       = {Lv, S. and Zhang Xiaoyan and others},
  title        = {{Deubiquitinase USP7 stabilizes the histone demethylase KDM5B and promotes the progression of renal fibrosis through the TSC1/mTOR axis}},
  journal      = {Molecular biomedicine},
  year         = {2026},
  doi          = {10.1186/s43556-026-00531-3},
  note         = {PMID: 42554966},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record LV2026S) [Data set]. https://mtor-atlas.org/study/LV2026S/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LV2026S,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LV2026S},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LV2026S/},
  doi          = {10.5281/zenodo.22059963}
}