2. Academic Validation
  3. TRIM36 inhibits lung fibroblast activation and pulmonary fibrosis through the degradation of phospho-AKT1

TRIM36 inhibits lung fibroblast activation and pulmonary fibrosis through the degradation of phospho-AKT1

  • iScience. 2025 Oct 15;28(11):113775. doi: 10.1016/j.isci.2025.113775.
Yajun Li 1,  Yuexia Yang 1,  Yingjie Wang 1,  Feifan Shi 1,  Yue Zhang 1,  Hongzhi Wen 1,  Xin Pan 1,  Cong Xia 1,  Zhongzheng Li 1,  Kaisa Cui 2,  Guojun Zhao 3,  Huibing Liu 1,  Qiwen Wang 1,  Lan Wang 1,  Guoying Yu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Organ Fibrosis, Institute of Biomedical Science, College of Life Science, Henan Normal University, Xinxiang, Henan 453000, P.R. China.
  • 2 Wuxi Cancer Institute, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214000, P.R. China.
  • 3 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
PMID: 41323265 DOI: 10.1016/j.isci.2025.113775
Abstract

The ubiquitin-proteasome system (UPS) critically regulates protein stability and function. E3 Ligase dysregulation plays a crucial role in idiopathic pulmonary fibrosis (IPF). TRIM36, a RING-finger E3 Ligase with emerging tumor-suppressive roles in various cancers, remains poorly characterized in IPF. In this study, we found that TRIM36 is significantly upregulated in IPF patients, and its expression is negatively associated with the disease severity. TRIM36 inhibits lung fibroblast proliferation, migration, and differentiation into myofibroblast in vitro. Mechanistically, TRIM36 mediates K48-linked polyubiquitination of phospho-AKT1 (T308/S473), leading to its proteasomal degradation and consequent inhibition of Akt signaling. Overexpression of TRIM36 markedly ameliorates bleomycin (BLM)-induced mouse pulmonary fibrosis. Taken together, these findings demonstrate that TRIM36 inhibits pulmonary fibrosis by degrading phospho-AKT1 (T308/S473) to inhibit Akt1 signaling, offering valuable insights for IPF treatment.

Keywords

Biochemistry; Cell biology; Disease; Fibrosis.

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