Genetic and non-genetic risk factors of idiopathic pulmonary fibrosis: A review

Shamil R. Zulkarneev¹, Rustem H. Zulkarneev^1*, Gulnaz Faritovna Korytina^2,3, Irshat A. Gibadullin⁴, Arthur M. Avzaletdinov⁴, Zhihui Niu⁵, Jiayu Guo⁵, Yulia Genadievna Aznabaeva¹, Guzel M. Nurtdinova¹, Naufal Shamilevich Zagidullin¹

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¹ Department of Internal Diseases, Bashkir State Medical University, Ufa, 450008, Russian Federation

² Institute of Biochemistry and Genetics - Subdivision of the Ufa Federal Research Centre of the Russian Academy of Sciences, IBG UFRC RAS, Laboratory of Physiological Genetics, Ufa, 450054, Russian Federation

³ Department of Biology, Bashkir State Medical University, Ufa, 450008, Russian Federation

⁴ Department of Hospital Surgery, Bashkir State Medical University, Republic of Bashkortostan, Ufa, 450008, Russian Federation

⁵ Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang 150081, China

Global Translational Medicine 2022, 1(2), 107 https://doi.org/10.36922/gtm.v1i2.107

Submitted: 22 May 2022 | Accepted: 2 September 2022 | Published: 26 September 2022

© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common form of fibrosis of internal organs. The etiology and pathogenesis of IPF are still not well understood. However, a growing line of evidence shows that both genetic and non-genetic factors contribute to IPF development. The release of pro-inflammatory cytokines activates the immune cells. The enhanced synthesis of interleukins and cytokines, especially transforming growth factor β1 leads to the proliferation of fibroblasts, increased extracellular matrix formation, and epithelial-mesenchymal transformation of the lung tissue. These pathological changes could lead to fibrosis. Polymorphisms of genes responsible for the function of mucociliary clearance (MUC5B), telomerases (TERT, TERC), as well as signaling pathway related-genes such as Sonic hedgehog, Wnt, and some other genes are also risk factors for IPF development. Epigenetic regulatory mechanisms, such as methylation and acetylation of DNA and histones, may also influence the development and progression of this disease. At present, the role of non-coding RNAs, in particular long non-coding RNAs (lncRNA) in the development of fibrotic processes, is actively studied. LncRNA is an RNA that is longer than 200 base pairs and does not code for any proteins. LncRNAs perform various functions in the cell, from nuclear compartmentation to epigenetic regulation of gene expression and post-translational modification of proteins. In this review, we present the important aspects in the pathogenesis of IPF.

Keywords

Long non-coding RNAs

Idiopathic pulmonary fibrosis

COVID-19-induced pulmonary fibrosis

Funding

Grant of Russian Scientific Foundation 22-25-00019

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None of the authors has conflicts of interest to report with regard to this manuscript.

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