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Micro‐RNA 203 Regulates Myometrial Smooth Muscle Cell Expression of the Transient Receptor Vanilloid 4 Channel
Author(s) -
Ying Lihua,
Barnes Elizabeth A,
Rodriguez Saidie,
Alvira Cristina M,
Cornfield David N
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb73
Subject(s) - trpv4 , transient receptor potential channel , myometrium , gene expression , transfection , microbiology and biotechnology , microrna , receptor , contraction (grammar) , inflammation , messenger rna , medicine , chemistry , endocrinology , gene , biology , uterus , biochemistry
Background We recently demonstrated that the expression and activity of the transient receptor vanilloid 4 (TRPV4) channel increase in myometrial smooth muscle cells (mSMC) during pregnancy. However, the molecular mechanisms that dynamically regulate TRPV4 expression and activity have not been identified. Accumulating evidence suggest that micro RNA molecules (miRNA) may influence the physiology of pregnancy by regulating the expression of molecules that affect implantation, uterine contraction, inflammation, and cervical remodeling. Although miR‐203 represses TRPV4 expression in chondrocytes, whether pregnancy associated changes in miR‐203 expression contribute to the heightened expression of TRPV4 in the pregnant myometrium remains unknown. Objective We hypothesized that with pregnancy, mSMC miR‐203 expression decreases as TRPV4 expression increases. Methods To test these hypotheses, miR‐203 and TRPV4 expression was determined by qPCR in primary mSMC isolated from non‐pregnant and pregnant (D18) mice. TRPV4 gene expression was also determined in human mSMC that were transfected with either non‐targeting control (NTC) or a miR‐203 mimetic. In separate studies, mSMC contraction was assessed in human mSMC transfected with either NTC or miR‐203 mimetic that were embedded in collagen gels. Results miR‐203 levels were almost 14‐fold higher in the non‐pregnant as compared to late pregnant mSMC (2.38±0.76 vs. 0.17±0.05, p=0.04). Treatment of human mSMC with the miR‐203 mimic increased miR‐203 expression by over 2000‐fold (p<0.0001), and decreased TRPV4 expression by approximately 90% (p=0.013). In addition, in the collagen gel assays, gels containing mSMC transfected with miR‐203 demonstrated an increase in area of 17% (p=0.016, versus control), consistent with relaxation. Conclusions These data demonstrate that in mSMC, miR‐203 suppresses TRPV4 gene expression. We speculate that reductions in miR‐203 expression during late gestation may allow for increased expression of TRPV4 near term, and represent a viable target to suppress uterine contractility, prolong pregnancy and prevent preterm delivery. Support or Funding Information Burroughs Wellcome Fund, Pretern Birth Intiative