Objective: This study was designed to evaluate the roles of microRNAs (miRNAs) in slow transit constipation (STC).
Design: All human tissue samples were from the of the colon. Expression of 372 miRNAs was examined in a discovery cohort of four patients with STC versus three age/sex-matched controls by a quantitative PCR array. Upregulated miRNAs were examined by quantitative reverse transcription qPCR (RT-qPCR) in a validation cohort of seven patients with STC and age/sex-matched controls. The effect of a highly differentially expressed miRNA on a custom human smooth muscle cell line was examined by RT-qPCR, electrophysiology, traction force microscopy, and ex vivo by lentiviral transduction in rat organotypic cultures.
Results: The expression of 13 miRNAs was increased in STC samples. Of those miRNAs, four were predicted to target , the gene that encodes the Na channel Na1.5. The expression of mRNA was decreased in STC samples. Let-7f significantly decreased Na current density in vitro in human smooth muscle cells. In rat organotypic cultures, overexpression of let-7f resulted in reduced frequency and amplitude of contraction.
Conclusions: A small group of miRNAs is upregulated in STC, and many of these miRNAs target the SCN5A-encoded Na channel Na1.5. Within this set, a novel Na1.5 regulator, let-7f, resulted in decreased Na1.5 expression, current density and reduced motility of GI smooth muscle. These results suggest Na1.5 and miRNAs as novel diagnostic and potential therapeutic targets in STC.
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http://dx.doi.org/10.1136/gutjnl-2019-318747 | DOI Listing |
Vet Med Sci
January 2025
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Ondokuz Mayis University, Samsun, Türkiye.
This study aimed to compare the inhibitory effect of flunixin meglumine and meloxicam on the smooth muscles of the gastrointestinal tract in male cattle. Tissue samples, including the abomasum, ileum, proximal loop and centripetal gyri of the ascending colon, were collected from routinely slaughtered male cattle. These samples were sectioned into strips and mounted in an isolated tissue bath system.
View Article and Find Full Text PDFCells
January 2025
Institute of Anatomy & Cell Biology, Faculty of Medicine, Justus-Liebig-University, Aulweg 123, 35392 Giessen, Germany.
Vascular smooth muscle cell (SMC) relaxation by guanylyl cyclases (GCs) and cGMP is mediated by NO and its receptor soluble GC (sGC) or natriuretic peptides (NPs) ANP/BNP and CNP with the receptors GC-A and GC-B, respectively. It is commonly accepted that cultured SMCs differ from those in intact vessels. Nevertheless, cell culture often remains the first step for signaling investigations and drug testing.
View Article and Find Full Text PDFCells
December 2024
School of Life Science, University of Technology Sydney, Ultimo, NSW 2007, Australia.
Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incurable airflow obstruction and chronic inflammation. Both TGF-β1 and CXCL8 have been well described as fundamental to COPD progression. DNA methylation and histone acetylation, which are well-understood epigenetic mechanisms regulating gene expression, are associated with COPD progression.
View Article and Find Full Text PDFJ Hypertens
December 2024
Institute for Fetology, The First Affiliated Hospital of Soochow University, Jiangsu.
Background: Paternal preconception alcohol exposure affects fetal development; however, it is largely unknown about the influences on offspring vasculature and mechanisms.
Methods: Offspring born form paternal rats treated with alcohol or water before pregnant was raised until 3 months of age. Vessel tone of mesenteric arteries was detected using myograph system; whole-cell calcium channel current in smooth muscle cells was tested using patch-clamp; molecule expressions were detected with real-time PCR, western blotting, and Dihydroethidium (DHE); DNA methylations were determined using targeted bisulfate sequencing assay.
Curr Eye Res
January 2025
Dr. Rolf M. Schwiete Center for Limbal Stem Cell and Congenital Aniridia Research, Saarland University, Saar, Germany.
Purpose: Our aim was to examine the expression of PAX6 and keratocyte-specific markers in human limbal stromal cells (LSCs) in congenital aniridia (AN) and in healthy corneas, .
Methods: Primary human LSCs were extracted from individuals with aniridia (AN-LSCs) ( = 8) and from healthy corneas (LSCs) ( = 8). The cells were cultured in either normal-glucose serum-containing cell culture medium (NGSC-medium) or low-glucose serum-free cell culture medium (LGSF-medium).
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