2. Academic Validation
  3. Tudor staphylococcal nuclease (Tudor-SN) regulates activation of quiescent hepatic stellate cells

Tudor staphylococcal nuclease (Tudor-SN) regulates activation of quiescent hepatic stellate cells

  • FEBS J. 2025 Mar 17. doi: 10.1111/febs.70073.
Baoxin Qian 1 2 3 4,  Yan Zhao 1 2 3,  Xinxin Zhang 1 2 3,  Chunyan Zhao 1 2 3 5,  Xiaoteng Cui 1 2 3,  Fengmei Wang 4 6,  Xiang Jing 7,  Lin Ge 1 2 3,  Zhi Yao 1 2 3,  Xingjie Gao 1 2 3,  Jie Yang 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Experimental Hematology, Key Laboratory of Cellular and Molecular Immunology in Tianjin, and Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, Key Laboratory of Breast Cancer Prevention and Therapy (Ministry of Education), Tianjin Medical University, China.
  • 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Tianjin Medical University, China.
  • 3 Department of Immunology, School of Basic Medical Science, Tianjin Medical University, China.
  • 4 Department of Gastroenterology and Hepatology, Nankai University Affinity the Third Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, China.
  • 5 Department of Medical Laboratory, Tianjin Hospital, Tianjin University, China.
  • 6 Tianjin Key Laboratory of Molecular Diagnosis and Treatment of Liver Cancer, Tianjin First Central Hospital, China.
  • 7 Department of Ultrasound, Nankai University Affinity the Third Central Hospital, Tianjin, China.
PMID: 40098321 DOI: 10.1111/febs.70073
Abstract

Several liver diseases have been associated with the Tudor staphylococcal nuclease (Tudor-SN) protein. Our previous results demonstrated that, in comparison to wild-type (WT) mice, systemic overexpression of Tudor-SN in transgenic (Tg) mice (Tudor-SN-Tg) ameliorates obesity-induced Insulin resistance and hepatic steatosis. In this study, we observed an inverse correlation in the expression levels of Tudor-SN and profibrogenic factors, such as alpha-smooth muscle actin (α-SMA) and collagen alpha-1(I) chain (COL1A1), in liver tissue samples between Tudor-SN-Tg and WT mice. The correlation was further validated in hepatic fibrotic tissues from patients with cirrhosis and fibrosis. Utilizing a carbon tetrachloride (CCl4)-induced hepatic fibrosis model, we observed that Tudor-SN attenuated hepatic fibrosis in mice. Tudor-SN was abundantly expressed in hepatic stellate cells (HSCs). In the Tudor-SN-Tg group, primary HSCs showed stellate-like morphology as well as reduced in vitro proliferation and chemotactic ability compared to the WT group. Pseudotime series analysis of HSCs further showed the role of Tudor-SN during the dynamic evolution of HSC activation. Reduced Tudor-SN expression facilitated the in vitro activation of LX-2 cells. Furthermore, primary HSC cells from WT and Tudor-SN knockout (KO) mice were isolated for RNA-sequencing analysis. The findings suggested that Tudor-SN may regulate the activation of primary HSCs by influencing lipid metabolism, translation initiation, immune response, and the extracellular matrix. In summary, we identified Tudor-SN as a newly identified regulator involved in the transition of quiescent HSCs to activated states, shedding light on the antifibrotic impact of Tudor-SN expression in the development of hepatic fibrosis.

Keywords

Tudor‐SN; activation; extracellular matrix; hepatic fibrosis; hepatic stellate cells.

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