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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1437540

Mechanisms underlying TRPV4-mediated regulation of miR-146a expression

Provisionally accepted
Bidisha Dutta Bidisha Dutta 1Manisha Mahanty Manisha Mahanty 1Kesavalu N. Lakshmyya Kesavalu N. Lakshmyya 2Shaik O. Rahaman Shaik O. Rahaman 1*
  • 1 University of Maryland, College Park, College Park, United States
  • 2 University of Florida, Gainesville, Florida, United States

The final, formatted version of the article will be published soon.

    Persistent inflammation is a major contributor in the development of various inflammatory diseases like atherosclerosis. Our study investigates how transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, interacts with microRNA-146a (miR-146a), within the context of inflammation and atherosclerosis. Micro-RNAs play a critical role in controlling gene expression, and miR-146a is notable for its anti-inflammatory actions. TRPV4 is activated by diverse soluble and mechanical stimuli, and often associated with inflammatory responses in various diseases. Here, we find that TRPV4 negatively regulates miR-146a expression in macrophages, especially following stimulation by lipopolysaccharides or alterations in matrix stiffness. We show that in atherosclerosis, a condition characterized by matrix stiffening, TRPV4 decreases miR-146a expression in aortic tissue macrophages. We find that TRPV4's impact on miR-146a is independent of activation of NFκB, Stat1, P38, and AKT, but is rather mediated through a mechanism involving histone deacetylation instead of DNA methylation at the miR-146a promoter site. Furthermore, we show that N-terminal residues 1 to 130 in TRPV4 is essential in suppression of miR-146a expression in LPS-stimulated macrophages. Altogether, this study identifies a regulatory mechanism of miR-146a expression by TRPV4 which may open new potential therapeutic strategies for managing inflammatory diseases.

    Keywords: MicroRNA-146a, Macrophages, Inflammation, Epigenetic regulation, TRPV4

    Received: 23 May 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Dutta, Mahanty, Lakshmyya and Rahaman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Shaik O. Rahaman, University of Maryland, College Park, College Park, United States

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