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CHI3L1 promotes myocardial fibrosis via regulating lncRNA TUG1/miR-495-3p/ETS1 axis

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Abstract

Abnormal levels of CHI3L1 and lnc TUG1 are often associated with myocardial fibrosis, and their specific expressions may be closely related to the process of myocardial fibrosis. In addition, CHI3L1 was found to significantly up-regulate the expression of lncTUG1. Therefore, this study further explored the major role of CHI3L1 in regulating the progression of myocardial fibrosis. Myocardial fibrosis in mice was established using an angiotensin (Ang II) model, and the degree of myocardial fibrosis was assessed by qPCR, western blot and pathological techniques. HL-1 cells with overexpression and silencing of CHI3L1 were constructed, and the cell migration ability was detected using the Transwell method. Biological information was used to predict the potential target miRNA of lnc TUG1, and the interaction between them was verified by dual luciferase reporter assay. Using functional rescue assay and the rAAV9 technique, CHI3L1 was verified to affect the fibrotic process of myocardial cells by regulating the lnc TUG1/miR-495-3p/ETS1 axis in vitro and in vivo. The myocardial fibrosis index in the model group was significantly upregulated, and expression of both CHI3L1 and lnc TUG1 was upregulated. Pathological results revealed fibrosis and collagen deposition in the myocardium. Overexpression of lnc TUG1 reversed the inhibitory effect of CHI3L1 silencing on myocardial fibrosis. Mechanistically, CH3L1 upregulates the expression of lnc TUG1, and lnc TUG1 weakens the inhibition of ETS1 through sponge absorption of miR-495-3p, promoting the process of myocardial fibrosis.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Cardiac Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin, 130021, China

    Yunpeng Sun, Xue Shan, Jiantao Guo, Xuguang Liu & Dashi Ma

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  1. Yunpeng Sun
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  2. Xue Shan
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  3. Jiantao Guo
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  4. Xuguang Liu
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Contributions

YP S, XG L and DS M carried out the studies, participated in collecting data, and drafted the manuscript. X S and JT G performed the statistical analysis and participated in its design. All authors read and approved the final manuscript.

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Correspondence to Xuguang Liu or Dashi Ma.

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All animal experiments conform to the standards of the Animal Ethics Committee. This study was approved by the ethics committee of The First Hospital of Jilin University (SY20191012).

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Sun, Y., Shan, X., Guo, J. et al. CHI3L1 promotes myocardial fibrosis via regulating lncRNA TUG1/miR-495-3p/ETS1 axis. Apoptosis 28, 1436–1451 (2023). https://doi.org/10.1007/s10495-023-01859-9

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  • DOI: https://doi.org/10.1007/s10495-023-01859-9

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