TGFβ signaling: its role in fibrosis formation and myopathies

Curr Opin Rheumatol. 2012 Nov;24(6):628-34. doi: 10.1097/BOR.0b013e328358df34.

Abstract

Purpose of review: Modifiers of TGFβ signaling have been investigated as treatment options for several types of muscle diseases. The purpose of this review is to focus on the most recent studies that have used this treatment strategy for pathological muscle disorders. We also review the recent insight into the mechanistic processes by which TGFβ signaling contributes to these pathologies by promoting fibrosis formation.

Recent findings: Recent research has shed light on the role of TGFβ signaling in the regulation of microRNAs associated with fibrosis formation. Inhibition of TGFβ signaling by Losartan treatment greatly improved the phenotype of myopathies associated with laminin-α2-deficient congenital muscular dystrophy. Caveolin 3 deficiency was also ameliorated by the use of several different types of TGFβ signaling inhibitors. Use of Losartan had dramatically beneficial effects on sarcopenic muscle by improving the regeneration after injury. Pharmacological manipulation to increase muscle mass is an emerging trend in obesity treatment research. New advances in the use of potent myostatin inhibitors have made this an attractive approach for future studies.

Summary: An increasing number of skeletal myopathies are demonstrating favorable responses to alterations of the TGFβ signaling pathway. However, future research is needed to fully understand the downstream molecular signature associated with this pathway in order to develop more specific targeted therapies.

Publication types

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

MeSH terms

  • Animals
  • Caveolin 3 / deficiency
  • Caveolin 3 / genetics
  • Disease Models, Animal
  • Fibrosis
  • Humans
  • Losartan / pharmacology
  • MicroRNAs / metabolism
  • Muscle, Skeletal / pathology*
  • Muscular Diseases / genetics
  • Muscular Diseases / metabolism*
  • Muscular Diseases / pathology
  • Muscular Dystrophies / drug therapy
  • Muscular Dystrophies / metabolism
  • Sarcopenia / genetics
  • Sarcopenia / metabolism
  • Signal Transduction / physiology*
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / metabolism*

Substances

  • Caveolin 3
  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Transforming Growth Factor beta
  • Losartan

Supplementary concepts

  • Muscular dystrophy congenital, merosin negative