Shexiang Tongxin Dropping Pretreated Mesenchymal Stem Cells-derived Exosomes Attenuate Cardiac Ischemia/Reperfusion Injury by Modulating miR-182-5p and miR-199a-3p-mediated Inflammatory Responses
Ling-Yan Li1, Ling-Fang Zhou1, Jia Shi1, Zong-Jun Liu1, Jun-Qing Gao1★★ Corresponding author
- 1Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
CORRESPONDENCE
Jun-Qing Gao
Department of Cardiology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Received: 06-04-2023; Accepted: 04-08-2023.
Volume 20, Issue 1 · pp. 291–302 · PUBLISHED 2024 · DOI: 10.1177/09731296231207232
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ABSTRACT
Background: Previous research has highlighted the regulatory role of miR-182-5p in targeting TLR4 during the pathogenesis of allergic rhinitis. In a different context, TLR4 has been identified as a crucial factor in the development of lung ischemiareperfusion injury, where its upregulation is believed to initiate the injury process. Additionally, miR-199a-3p has been shown to possess cardioprotective properties in simulated ischemia/reperfusion (I/R) injury models. Materials and Methods: HE and TUNEL were performed to evaluate the cardiac injury and cellular apoptosis of I/R mice under distinct conditions. Real-time PCR was used to analyze the expression of microRNAs (miRNAs) and mRNAs under differential conditions. Results: Pretreatment by Shexiang Tongxin Dropping (SXTXD) has been shown to significantly augment the therapeutic efficacy of MSC-derived exosomes (MSC-EXOs) in attenuating cardiac injury in I/R mice. MSC-EXOs effectively restored the repressed miR-182/miR-199a-3p expressions and activated TLR4/CD44 expressions in I/R mice, while SXTXD pretreatment remarkably strengthened the efficiency of MSC-EXOs. Moreover, SXTXD pretreatment notably reinforced the capability of MSC-EXOs to maintain cardiac parameters, including iNOS and interleukin-1β (IL-1β). Furthermore, the luciferase assay indicated that miR-182-5p and miR-199a-3p effectively suppressed the luciferase activities of TLR4 and CD44, respectively, through binding to the 3´ UTR. The overexpression of miR-182-5p and miR-199a-3p significantly suppressed the expression of TLR4 and CD44 in H2C6 and RAW264.7 cells. Conclusion: In conclusion, our investigation indicates that MSC-derived exosomes, pretreated with SXTXD, hold promise in mitigating cardiac I/R injury by modulating inflammatory responses through the miR-182-5p/TLR4 axis and miR-199a-3p/ CD44 axis. These findings suggest potential therapeutic strategies for addressing I/R-related cardiac complications.
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Li, L., Zhou, L., Shi, J., Liu, Z., & Gao, J. (2024). Shexiang Tongxin Dropping Pretreated Mesenchymal Stem Cells-derived Exosomes Attenuate Cardiac Ischemia/Reperfusion Injury by Modulating miR-182-5p and miR-199a-3p-mediated Inflammatory Responses. Pharmacognosy Magazine, 20(1), 291–302. https://doi.org/10.1177/09731296231207232