The Role of the Mammalian Target of Rapamycin (mTOR) in Pulmonary Fibrosis

Int J Mol Sci. 2018 Mar 8;19(3):778. doi: 10.3390/ijms19030778.

Abstract

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-dependent pathway is one of the most integral pathways linked to cell metabolism, proliferation, differentiation, and survival. This pathway is dysregulated in a variety of diseases, including neoplasia, immune-mediated diseases, and fibroproliferative diseases such as pulmonary fibrosis. The mTOR kinase is frequently referred to as the master regulator of this pathway. Alterations in mTOR signaling are closely associated with dysregulation of autophagy, inflammation, and cell growth and survival, leading to the development of lung fibrosis. Inhibitors of mTOR have been widely studied in cancer therapy, as they may sensitize cancer cells to radiation therapy. Studies also suggest that mTOR inhibitors are promising modulators of fibroproliferative diseases such as idiopathic pulmonary fibrosis (IPF) and radiation-induced pulmonary fibrosis (RIPF). Therefore, mTOR represents an attractive and unique therapeutic target in pulmonary fibrosis. In this review, we discuss the pathological role of mTOR kinase in pulmonary fibrosis and examine how mTOR inhibitors may mitigate fibrotic progression.

Keywords: fibrosis; idiopathic pulmonary fibrosis (IPF); mammalian target of rapamycin (mTOR); phosphoinositide 3-kinase (PI3K); protein kinase B (AKT); radiation-induced pulmonary fibrosis (RIPF).

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins c-akt / metabolism
  • Pulmonary Fibrosis / drug therapy
  • Pulmonary Fibrosis / metabolism*
  • Signal Transduction
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases