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Current Respiratory Medicine Reviews


ISSN (Print): 1573-398X
ISSN (Online): 1875-6387

Review Article

Local Lung Fibroblast Autophagy in the Context of Lung Fibrosis Pathogenesis

Author(s): Basheer Abdullah Marzoog*

Volume 19, Issue 1, 2023

Published on: 26 December, 2022

Page: [6 - 11] Pages: 6

DOI: 10.2174/1573398X19666221130141600

Price: $65


The current molecular advances in lung fibrosis pathogenesis distend beyond the cellular to involve subcellular and molecular levels. Lung fibrogenesis and autophagy impairment are tightly associated. Autophagy is involved in cell cycle control and regulation of the intracellular microenvironment. Degradation of impaired intracellular organelles and biproducts is crucial to maintaining a healthy cell and preventing its metaplasia / transdifferentiation to a pathological cell. Autophagy modifies the metabolism of alveolar epithelial cells, endothelial cells, and lung fibroblasts. Autophagy upregulation induces local lung fibroblast hyperactivity and fibrosis. Several molecular triggers were found to induce lung fibroblast autophagy including TGFβ by inhibition of the PI3K/AKT/mTOR. However, physiologically, a balance is retained between autophagy inducers and inhibitors. Each type of autophagy plays its role in the initiation and progression of lung fibrosis. The pathogenesis of pulmonary fibrosis is multifactorial and involves dysfunction / dysregulation of alveolar epithelial cells, fibroblasts, monocyte-derived macrophages, and endothelial cells. The deposition of extracellular matrix proteins, the remodeling of the lung architecture and the molecular changes include impaired glycolysis, mitochondrial oxidation, gene expression modification, altered phospholipid and sphingolipid metabolism, and dysregulated protein folding lead to reprogramming of lung fibroblast into myofibroblast and their activation. The paper thoroughly addresses the molecular triggers and inhibitors of lung fibroblast autophagy in lung fibrosis.

Keywords: Autophagy, pathogenesis, pulmonary fibrosis, cytokines, TGF-β1, pathogenetic therapy.

Graphical Abstract
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