Role of microRNAs in gastrointestinal smooth muscle fibrosis and dysfunction: novel molecular perspectives on the pathophysiology and therapeutic targeting

Am J Physiol Gastrointest Liver Physiol. 2016 Apr 1;310(7):G449-59. doi: 10.1152/ajpgi.00445.2015. Epub 2016 Jan 28.

Abstract

MicroRNAs (miRNAs) belong to a group of short noncoding RNA molecules with important roles in cellular biology. miRNAs regulate gene expression by repressing translation or degrading the target mRNA. Recently, a growing body of evidence suggests that miRNAs are implicated in many diseases and could be potential biomarkers. Fibrosis and/smooth muscle (SM) dysfunction contributes to the morbidity and mortality associated with several diseases of the gastrointestinal tract (GIT). Currently available therapeutic modalities are unsuccessful in efficiently blocking or reversing fibrosis and/or SM dysfunction. Recent understanding of the role of miRNAs in signaling pathway of fibrogenesis and SM phenotype switch has provided a new insight into translational research. However, much is still unknown about the molecular targets and therapeutic potential of miRNAs in the GIT. This review discusses miRNA biology, pathophysiology of fibrosis, and aging- associated SM dysfunction in relation to the deregulation of miRNAs in the GIT. We also highlight the role of selected miRNAs associated with fibrosis and SM dysfunction-related diseases of the GIT.

Keywords: cellular and epigenetic mechanisms; inflammatory mediators; microRNA; phenotypic plasticity; rho kinase; smooth muscle fibrosis; smooth muscle phenotypic switch.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Epigenesis, Genetic
  • Fibrosis
  • Gastrointestinal Diseases / genetics
  • Gastrointestinal Diseases / metabolism*
  • Gastrointestinal Diseases / physiopathology
  • Gastrointestinal Diseases / therapy
  • Gastrointestinal Tract / metabolism*
  • Gastrointestinal Tract / pathology
  • Gastrointestinal Tract / physiopathology
  • Gene Expression Regulation
  • Genetic Markers
  • Genetic Therapy / methods
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • MicroRNAs / therapeutic use
  • Muscle, Smooth / metabolism*
  • Muscle, Smooth / pathology
  • Muscle, Smooth / physiopathology
  • Oxidative Stress
  • Phenotype
  • Signal Transduction

Substances

  • Genetic Markers
  • MicroRNAs