Journal
EXPERIMENTAL CELL RESEARCH
Volume 399, Issue 2, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2020.112464
Keywords
Diabetic cardiac fibrosis; Cardiac fibroblast; Androgen receptor; miR-21-3p
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Funding
- National Natural Science Foundation of China [81700212]
- Natural Science Foundation of Anhui Provincial [1808085MH231]
- National Natural Science Foundation Incubation Program of the Second Affiliated Hospital of Anhui Medical University [2020GMFY02]
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Our study demonstrated that miR-21-3p exacerbates STZ-induced diabetic cardiac fibrosis through the caspasel pathways by suppressing AR expression, leading to cardiac fibroblasts pyroptosis and collagen deposition.
Aims/hypothesis: MicroRNA-21 has been implicated in diabetic complication, including diabetic cardiomyopathy. However, there is limited information regarding the biological role of the miR-21 passenger strand (miR-21-3p) in diabetic cardiac fibrosis. The aim of this study was to investigate the role of miR-21-3p and its target androgen receptor in STZ-induced diabetic cardiac fibrosis. Methods: The pathological changes and collagen depositions was analyzed by HE, Sirius Red staining and Masson's Trichrome Staining. MiR-21-3p, AR, NLRP3, caspasel and collagen I expression were analyzed by western blotting, immunohistochemistry, immunofluorescence, qRT-PCR, miR one step qRT-PCR, respectively. A luciferase reporter assay was used to verify the interaction between miR-21 and the 3' untranslated region (3'UTR) of AR. Results: Our results indicated that miR-21-3p level was up-regulated, while AR was decreased in STZ-induced diabetic cardiac fibrosis tissues and cardiac fibroblast. High glucose triggers cardiac fibroblasts pyroptosis and collagen deposition. Gain-of-function and loss-of-function assays demonstrated that miR-21-3p mediated the crucial role in diabetic cardiac fibrosis. Our results show that miR-21-3p bound to the 3'UTR of AR posttranscriptionally repressed its expression. We also found AR, which regulates cardiac fibroblasts pyroptosis and collagen deposition through caspasel signaling. Conclusions: /interpretation: Taken together, our study showed that miR-21-3p aggravates STZ-induced diabetic cardiac fibrosis through the caspasel pathways by suppressing AR expression.
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