2. Academic Validation
  3. Sulodexide attenuates liver fibrosis in mice by restoration of differentiated liver sinusoidal endothelial cell

Sulodexide attenuates liver fibrosis in mice by restoration of differentiated liver sinusoidal endothelial cell

  • Biomed Pharmacother. 2023 Apr:160:114396. doi: 10.1016/j.biopha.2023.114396.
Ru Huang 1,  Juan Deng 1,  Chang-Peng Zhu 2,  Shu-Qing Liu 2,  Ya-Lu Cui 2,  Fei Chen 2,  Xin Zhang 2,  Xia Tao 3,  Wei-Fen Xie 4
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
  • 2 Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China.
  • 3 Department of Pharmacology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China. Electronic address: taoxia@smmu.edu.cn.
  • 4 Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200092, China; Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai 200003, China; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai 200120, China. Electronic address: weifenxie@medmail.com.cn.
PMID: 36791568 DOI: 10.1016/j.biopha.2023.114396
Abstract

Sulodexide is a heparinoid compound with wide-ranging pharmacological activities. However, the effect of sulodexide on liver fibrogenesis has not been reported. In this study, we aim to evaluate the therapeutic potential of sulodexide in mouse model of liver fibrosis and explore the underlying antifibrotic mechanisms. We found that sulodexide treatment significantly attenuated thioacetamide (TAA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced liver fibrosis in mice. Transcriptome analysis revealed that sulodexide treatment downregulated fibrosis-related genes and liver sinusoidal endothelial cells (LSECs) capillarization-associated genes in fibrotic livers. Immunohistochemistry confirmed that the increased expression of LSEC capillarization-related genes (CD34, CD31 and Laminin) in liver fibrotic tissues was reduced by sulodexide treatment. Scanning electron microscopy showed that LSECs fenestrations were preserved upon sulodexide treatment. Quantitative Real-Time PCR and immunofluorescence demonstrated that the expression of mesenchymal markers was downregulated by sulodexide administration, suggesting sulodexide inhibited endothelial-mesenchymal transition of LSECs during liver fibrosis. Furthermore, sulodexide administration protected primary LSECs from endothelial dysfunction in vitro. In conclusion, sulodexide attenuated liver fibrosis in mice by restoration of differentiated LSECs, indicating that sulodexide treatment may present as a potential therapy for patients with liver fibrosis.

Keywords

Anticoagulants; Endothelial dysfunction; Endothelial-mesenchymal transition; Liver fibrosis; Liver sinusoidal endothelial cell capillarization; Sulodexide.

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