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Updated: May 4, 2026

Single-channel Analysis and Calcium Imaging in the Podocytes of the Freshly Isolated Glomeruli
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USP22 promotes angiotensin II-induced podocyte injury by deubiquitinating and stabilizing HMGB1

Zhuan Peng1, Xiaoxiao Huang1, Yangbin Pan2

  • 1Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.

Cellular Signalling
|March 28, 2025
PubMed

Insights

Ubiquitin-specific protease 22 (USP22) drives kidney damage in hypertensive nephropathy by stabilizing HMGB1. Inhibiting USP22 protects podocytes and improves kidney function, offering a new therapeutic target for chronic kidney disease.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Hypertensive nephropathy (HN) is a major cause of chronic kidney disease (CKD), characterized by podocyte injury.
  • The precise molecular mechanisms of angiotensin II-induced podocyte damage in HN are not fully understood.
  • Ubiquitin-specific protease 22 (USP22) is implicated in cellular processes, but its role in HN is unknown.

Purpose of the Study:

  • To investigate the role of USP22 in angiotensin II-induced podocyte injury and inflammation in hypertensive nephropathy.
  • To identify the molecular mechanisms by which USP22 contributes to HN pathogenesis.
  • To evaluate the therapeutic potential of targeting the USP22-HMGB1 axis in HN.

Main Methods:

  • Assessed USP22 expression in HN patients, angiotensin II-induced mouse models, and cultured podocytes.
  • Utilized podocyte-specific USP22 knockout mice to examine the impact of USP22 deletion.
  • Investigated the interaction between USP22 and high-mobility group box protein 1 (HMGB1).

Main Results:

  • USP22 expression was significantly elevated in HN kidneys, models, and podocytes.
  • USP22 knockout in podocytes attenuated angiotensin II-induced injury and inflammation.
  • USP22 deubiquitinates and stabilizes HMGB1; reducing USP22 promotes HMGB1 degradation, improving kidney function.

Conclusions:

  • USP22 is a critical regulator of angiotensin II-induced podocyte injury and inflammation via HMGB1.
  • Targeting the USP22-HMGB1 pathway presents a potential therapeutic strategy for hypertensive nephropathy and CKD.
Abstract

Keywords:
Angiotensin IIChronic kidney diseaseHMGB1Hypertensive nephropathyPodocyte injuryUSP22

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