Telomere Dysfunction in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis is an age-dependent progressive and fatal lung disease of unknown etiology, which is characterized by the excessive accumulation of extracellular matrix inside the interstitial layer of the lung parenchyma that leads to abnormal scar architecture and compromised lung fu...

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Autores principales:	Kexiong Zhang, Lu Xu, Yu-Sheng Cong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	telomere dysfunction telomere shortening alveolar stem cells SASP innate immune cells TGF-β Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f74e796df5be456aab48ef789baf46ce
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spelling	oai:doaj.org-article:f74e796df5be456aab48ef789baf46ce2021-11-11T06:20:10ZTelomere Dysfunction in Idiopathic Pulmonary Fibrosis2296-858X10.3389/fmed.2021.739810https://doaj.org/article/f74e796df5be456aab48ef789baf46ce2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.739810/fullhttps://doaj.org/toc/2296-858XIdiopathic pulmonary fibrosis is an age-dependent progressive and fatal lung disease of unknown etiology, which is characterized by the excessive accumulation of extracellular matrix inside the interstitial layer of the lung parenchyma that leads to abnormal scar architecture and compromised lung function capacity. Recent genetic studies have attributed the pathological genes or genetic mutations associated with familial idiopathic pulmonary fibrosis (IPF) and sporadic IPF to telomere-related components, suggesting that telomere dysfunction is an important determinant of this disease. In this study, we summarized recent advances in our understanding of how telomere dysfunction drives IPF genesis. We highlighted the key role of alveolar stem cell dysfunction caused by telomere shortening or telomere uncapping, which bridged the gap between telomere abnormalities and fibrotic lung pathology. We emphasized that senescence-associated secretory phenotypes, innate immune cell infiltration, and/or inflammation downstream of lung stem cell dysfunction influenced the native microenvironment and local cell signals, including increased transforming growth factor-beta (TGF-β) signaling in the lung, to induce pro-fibrotic conditions. In addition, the failed regeneration of new alveoli due to alveolar stem cell dysfunction might expose lung cells to elevated mechanical tension, which could activate the TGF-β signaling loop to promote the fibrotic process, especially in a periphery-to-center pattern as seen in IPF patients. Understanding the telomere-related molecular and pathophysiological mechanisms of IPF would provide new insights into IPF etiology and therapeutic strategies for this fatal disease.Kexiong ZhangLu XuYu-Sheng CongFrontiers Media S.A.articletelomere dysfunctiontelomere shorteningalveolar stem cellsSASPinnate immune cellsTGF-βMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	telomere dysfunction telomere shortening alveolar stem cells SASP innate immune cells TGF-β Medicine (General) R5-920
spellingShingle	telomere dysfunction telomere shortening alveolar stem cells SASP innate immune cells TGF-β Medicine (General) R5-920 Kexiong Zhang Lu Xu Yu-Sheng Cong Telomere Dysfunction in Idiopathic Pulmonary Fibrosis
description	Idiopathic pulmonary fibrosis is an age-dependent progressive and fatal lung disease of unknown etiology, which is characterized by the excessive accumulation of extracellular matrix inside the interstitial layer of the lung parenchyma that leads to abnormal scar architecture and compromised lung function capacity. Recent genetic studies have attributed the pathological genes or genetic mutations associated with familial idiopathic pulmonary fibrosis (IPF) and sporadic IPF to telomere-related components, suggesting that telomere dysfunction is an important determinant of this disease. In this study, we summarized recent advances in our understanding of how telomere dysfunction drives IPF genesis. We highlighted the key role of alveolar stem cell dysfunction caused by telomere shortening or telomere uncapping, which bridged the gap between telomere abnormalities and fibrotic lung pathology. We emphasized that senescence-associated secretory phenotypes, innate immune cell infiltration, and/or inflammation downstream of lung stem cell dysfunction influenced the native microenvironment and local cell signals, including increased transforming growth factor-beta (TGF-β) signaling in the lung, to induce pro-fibrotic conditions. In addition, the failed regeneration of new alveoli due to alveolar stem cell dysfunction might expose lung cells to elevated mechanical tension, which could activate the TGF-β signaling loop to promote the fibrotic process, especially in a periphery-to-center pattern as seen in IPF patients. Understanding the telomere-related molecular and pathophysiological mechanisms of IPF would provide new insights into IPF etiology and therapeutic strategies for this fatal disease.
format	article
author	Kexiong Zhang Lu Xu Yu-Sheng Cong
author_facet	Kexiong Zhang Lu Xu Yu-Sheng Cong
author_sort	Kexiong Zhang
title	Telomere Dysfunction in Idiopathic Pulmonary Fibrosis
title_short	Telomere Dysfunction in Idiopathic Pulmonary Fibrosis
title_full	Telomere Dysfunction in Idiopathic Pulmonary Fibrosis
title_fullStr	Telomere Dysfunction in Idiopathic Pulmonary Fibrosis
title_full_unstemmed	Telomere Dysfunction in Idiopathic Pulmonary Fibrosis
title_sort	telomere dysfunction in idiopathic pulmonary fibrosis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f74e796df5be456aab48ef789baf46ce
work_keys_str_mv	AT kexiongzhang telomeredysfunctioninidiopathicpulmonaryfibrosis AT luxu telomeredysfunctioninidiopathicpulmonaryfibrosis AT yushengcong telomeredysfunctioninidiopathicpulmonaryfibrosis
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Telomere Dysfunction in Idiopathic Pulmonary Fibrosis

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