Establishment of a mouse model of vascular endothelial-mesenchymal transdifferentiation genetic tracing and its role in liver fibrosis studies

Hao XU; Bai RUAN; Zhiwen LI; Zhiqiang FANG; Lin WANG; Kefeng DOU

doi:10.3969/j.issn.1001-5256.2022.04.018

Volume 38 Issue 4

Apr. 2022

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Article Navigation > Journal of Clinical Hepatology > 2022 > 38(4): 832-836

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Establishment of a mouse model of vascular endothelial-mesenchymal transdifferentiation genetic tracing and its role in liver fibrosis studies

DOI: 10.3969/j.issn.1001-5256.2022.04.018

Hao XU¹,
Bai RUAN^{1, 2},
Zhiwen LI¹,
Zhiqiang FANG¹,
Lin WANG¹,
Kefeng DOU^{1
,
,
,}

1.
Department of Hepatobiliary, Pancreatic and Splenic Surgery, Xijing Hospital, Air Force Medical University, Xi'an 710032, China
2.
Center of Clinical Aerospace Medicine, School of Aerospace Medicine, Air Force Medical University, Xi'an 710032, China

Research funding:

The National Key Research and Development Program of China (2016YFA0102100);

National Natural Science Foundation of China (81770560);

National Natural Science Foundation of China (81800533)

More Information

Corresponding author: DOU Kefeng, doukef@fmmu.edu.cn (ORCID: 0000-0002-8857-5663)
Received Date: 2021-10-26
Accepted Date: 2021-11-28
Published Date: 2022-04-20

Abstract

Abstract

Objective To establish Cdh5-Cre^ERT/Acta2-tdTomato-STOP^floxed-eGFP knockin genetic tracing mice, and to investigate its application in studies on vascular endothelial cell transition in liver fibrosis. Methods Cdh5-Cre^ERT mice were mated with Acta2-KI mice, and the Cdh5-Cre^ERT/Acta2-KI genetic tracing mice were obtained and identified by PCR genotyping. Primary liver sinusoid endothelial cells (LSECs) were isolated and cultured, and a model of CCl₄-induced liver fibrosis was established. LSECs and liver tissue were collected for immunofluorescent staining to observe the expression of the fluorescent proteins tdTomato and eGFP. Results After being induced by tamoxifen, LSECs and liver tissue of Cdh5-Cre^ERT/Acta2-KI genetic tracing mice expressed eGFP under the conditions for epithelial-mesenchymal transdifferentiation established in vivo and in vitro, while the control group without induction expressed tdTomato alone. Conclusion The successfully established Cdh5-Cre^ERT/Acta2-KI genetic tracing mice can realize the effective labeling of epithelial-mesenchymal transdifferentiation, which provides a genetic tracing basis for the diverse sources of mesenchymal myofibroblasts in liver fibrosis.
- Liver Cirrhosis,
- Epithelial-Mesenchymal Transition,
- Endothelial Cells,
- Mice

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Establishment of a mouse model of vascular endothelial-mesenchymal transdifferentiation genetic tracing and its role in liver fibrosis studies

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Establishment of a mouse model of vascular endothelial-mesenchymal transdifferentiation genetic tracing and its role in liver fibrosis studies

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