The role of the mammalian target of rapamycin (mTOR) in pulmonary fibrosis

Jessica Lawrence, Richard Nho

Research output: Contribution to journalReview articlepeer-review

61 Scopus citations

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.

Original languageEnglish (US)
Article number778
JournalInternational journal of molecular sciences
Volume19
Issue number3
DOIs
StatePublished - Mar 8 2018

Bibliographical note

Funding Information:
Acknowledgments: This study was supported by the NHLBI HL114662 (RN).

Funding Information:
This study was supported by the NHLBI HL114662 (RN).

Publisher Copyright:
© 2018 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Fibrosis
  • Idiopathic pulmonary fibrosis (IPF)
  • Mammalian target of rapamycin (mTOR)
  • Phosphoinositide 3-kinase (PI3K)
  • Protein kinase B (AKT)
  • Radiation-induced pulmonary fibrosis (RIPF)

Fingerprint

Dive into the research topics of 'The role of the mammalian target of rapamycin (mTOR) in pulmonary fibrosis'. Together they form a unique fingerprint.

Cite this