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- W4283779902 abstract "Abstract Background & aims Visceral smooth muscle cells (SMCs) are an integral component of the gastrointestinal (GI) tract and are critical for regulating motility. SMC contraction is regulated by changes in post-translational signaling and the state of differentiation. Impaired SMC contraction is associated with significant morbidity and mortality but the mechanisms regulating the expression levels of SMC-specific contractile proteins, including the role of long non-coding RNAs (lncRNAs), remains largely unexplored. Herein, we have uncovered an important role of Carmn (Cardiac mesoderm enhancer-associated noncoding RNA), a SMC-specific lncRNA, in regulating the phenotype of visceral SMCs of the GI tract. Methods Analysis of GTEx and publicly available single-cell RNA sequencing (scRNA-seq) datasets from embryonic, adult human and mouse GI tissues were used to identify SMC-specific lncRNAs. The functional role of Carmn was investigated using a novel GFP knock-in (KI) reporter/knockout (KO) mouse model. Bulk RNA sequencing (RNA-seq) and single nuclei RNA sequencing (snRNA-seq) of colonic muscularis were used to investigate underlying mechanisms. Results Unbiased in silico analyses and GFP expression patterns in Carmn GFP KI mice revealed that Carmn is specifically expressed in SMCs in human and mouse GI tract. Premature lethality was observed in global Carmn KO (gKO) and inducible SMC-specific KO (iKO) mice due to colonic pseudo-obstruction, severe distension of the GI tract with blockages in cecum and colon segments. Histology, whole-gut GI transit time and muscle myography analysis revealed severe dilation, significantly delayed GI transit and impaired GI contractility in Carmn KO mice versus control mice. Bulk RNA-seq of colonic muscularis revealed that Carmn deficiency promotes SMC de-differentiation as evidenced by up-regulation of extracellular matrix genes and down-regulation of SMC contractile genes including Mylk , a key regulator of SMC contraction. SnRNA-seq further revealed SMC Carmn deficiency not only compromised myogenic motility by reducing expression of contractile genes but also impaired neurogenic motility by disrupting cell-cell connectivity in the colonic muscularis. These findings may have translational significance as silencing CARMN in human colonic SMCs significantly attenuated contractile gene expression including MYLK and decreased SMC contractility. Luciferase reporter assays showed that CARMN enhances the transactivation activity of the master regulator of SMC contractile phenotype, myocardin, thereby maintaining the GI SMC myogenic program. Conclusion Our data suggest that Carmn is indispensable for maintaining GI SMC contractile function in mice, and that loss of function of CARMN may contribute to human visceral myopathy. To our knowledge this is the first study showing an essential role of lncRNA in the regulation of visceral SMC phenotype." @default.
- W4283779902 created "2022-07-03" @default.
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- W4283779902 date "2022-06-30" @default.
- W4283779902 modified "2023-09-24" @default.
- W4283779902 title "The LncRNA <i>Carmn</i> is a Critical Regulator for Gastrointestinal Smooth Muscle Contractile Function and Motility" @default.
- W4283779902 cites W1968963646 @default.
- W4283779902 cites W1977902242 @default.
- W4283779902 cites W1982747556 @default.
- W4283779902 cites W1984883254 @default.
- W4283779902 cites W1988011192 @default.
- W4283779902 cites W2012169418 @default.
- W4283779902 cites W2018621592 @default.
- W4283779902 cites W2019832656 @default.
- W4283779902 cites W2043278995 @default.
- W4283779902 cites W2046372092 @default.
- W4283779902 cites W2051889170 @default.
- W4283779902 cites W2054542819 @default.
- W4283779902 cites W2058326064 @default.
- W4283779902 cites W2058817142 @default.
- W4283779902 cites W2080149738 @default.
- W4283779902 cites W2086545594 @default.
- W4283779902 cites W2087210129 @default.
- W4283779902 cites W2096628719 @default.
- W4283779902 cites W2103680698 @default.
- W4283779902 cites W2104010513 @default.
- W4283779902 cites W2105756003 @default.
- W4283779902 cites W2108661174 @default.
- W4283779902 cites W2118180577 @default.
- W4283779902 cites W2122669364 @default.
- W4283779902 cites W2129282525 @default.
- W4283779902 cites W2138742704 @default.
- W4283779902 cites W2144545083 @default.
- W4283779902 cites W2148411491 @default.
- W4283779902 cites W2152948086 @default.
- W4283779902 cites W2159903983 @default.
- W4283779902 cites W2160831363 @default.
- W4283779902 cites W2165608965 @default.
- W4283779902 cites W2171559697 @default.
- W4283779902 cites W2172151945 @default.
- W4283779902 cites W2192025959 @default.
- W4283779902 cites W2315863900 @default.
- W4283779902 cites W2480373428 @default.
- W4283779902 cites W2531927236 @default.
- W4283779902 cites W2561955917 @default.
- W4283779902 cites W2582033455 @default.
- W4283779902 cites W2583659714 @default.
- W4283779902 cites W2601724561 @default.
- W4283779902 cites W2621822292 @default.
- W4283779902 cites W2747877289 @default.
- W4283779902 cites W2766554620 @default.
- W4283779902 cites W2790918267 @default.
- W4283779902 cites W2793027246 @default.
- W4283779902 cites W2800608949 @default.
- W4283779902 cites W2888247702 @default.
- W4283779902 cites W2892688552 @default.
- W4283779902 cites W2905639168 @default.
- W4283779902 cites W2914805278 @default.
- W4283779902 cites W2965448013 @default.
- W4283779902 cites W2973507295 @default.
- W4283779902 cites W3086918227 @default.
- W4283779902 cites W3110852430 @default.
- W4283779902 cites W3111853778 @default.
- W4283779902 cites W3115880421 @default.
- W4283779902 cites W3120659488 @default.
- W4283779902 cites W3129865120 @default.
- W4283779902 cites W3132661792 @default.
- W4283779902 cites W3133859624 @default.
- W4283779902 cites W3133897636 @default.
- W4283779902 cites W3137110961 @default.
- W4283779902 cites W3186716050 @default.
- W4283779902 cites W3198796616 @default.
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- W4283779902 doi "https://doi.org/10.1101/2022.06.28.498024" @default.
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