Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Aug 16;25(16):8946.
doi: 10.3390/ijms25168946.

Cellular and Molecular Genetic Mechanisms of Lung Fibrosis Development and the Role of Vitamin D: A Review

Darya Enzel  1 , Maxim Kriventsov  1 , Tatiana Sataieva  1 , Veronika Malygina  1
Affiliations
Review

Cellular and Molecular Genetic Mechanisms of Lung Fibrosis Development and the Role of Vitamin D: A Review

Darya Enzel et al. Int J Mol Sci. .

Abstract

Idiopathic pulmonary fibrosis remains a relevant problem of the healthcare system with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the damage of the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD-mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of new approaches aimed at regulating the immune response, cellular aging processes, programmed cell death, and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential _targets, and effects of vitamin D and its metabolites.

Keywords: fibrosis; inflammation; lungs; vitamin D; vitamin D receptors.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Diagram of some interactions between vitamin D and T cells. Vitamin D and its metabolites suppress cytokines related to proinflammatory Th1 and Th17 immune responses but stimulate secretion of cytokines associated with Th2 and Treg. The scheme was generated using images from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/), accessed on 10 July 2024 Abbreviations: Vit D—vitamin D and its metabolites; IL—interleukins; Th1—T-helper type 1; Th2—T-helper type 2; Th17—T-helper type 17; Treg—regulatory T-cell; IFNγ—interferon gamma; TNF-α—tumor necrosis factor alpha. Solid arrows—stimulation/enhancing effects; dashed arrows—inhibitory effects.
Figure 2
Figure 2
Diagram of the key mechanisms of pulmonary fibrosis development and potential application points for the effects of vitamin D and its metabolites. Initiated by damage to alveolocytes, pulmonary fibrosis is mediated by a proinflammatory response with dysregulatory excess extracellular matrix deposition. Possible effects of vitamin D and its metabolites/VDR may include inhibition of the secretion of proinflammatory cytokines (IL-1β and TGF-β), including by suppressing the renin–angiotensin system (a); suppression of the epithelial–mesenchymal transition (b); modulation of the polarization of macrophages on M1 and M2 subpopulations (c); an increase in the subpopulation of Th2 cells and a shift from Th17 towards T-regulatory cells (d,e). The scheme was generated using images from Servier Medical Art. Servier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License (https://creativecommons.org/licenses/by/3.0/), accessed on 10 July 2024. Abbreviations: SASP (senescence-associated secretory phenotype)—cellular phenotype associated with aging; EMT—epithelial–mesenchymal transition; TNF-a—tumor necrosis factor alpha; TGF-β—transforming growth factor beta; PDGF—platelet growth factor; a-SMA—smooth muscle actin alpha; IL—interleukins; MMP—metalloproteinases; NET—neutrophil extracellular trap; Th1—T-helper type 1; Th2—T-helpers type 2; Th17—T-helpers type 17; VDR—vitamin D receptor.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Mei Q., Liu Z., Zuo H., Yang Z., Qu J. Idiopathic Pulmonary Fibrosis: An Update on Pathogenesis. Front. Pharmacol. 2022;12:797292. doi: 10.3389/fphar.2021.797292. - DOI - PMC - PubMed
    1. Glass D.S., Grossfeld D., Renna H.A., Agarwala P., Spiegler P., DeLeon J., Reiss A.B. Idiopathic Pulmonary Fibrosis: Current and Future Treatment. Clin. Respir. J. 2022;16:84–96. doi: 10.1111/crj.13466. - DOI - PMC - PubMed
    1. Zheng Q., Cox I.A., Campbell J.A., Xia Q., Otahal P., De Graaff B., Corte T.J., Teoh A.K.Y., Walters E.H., Palmer A.J. Mortality and Survival in Idiopathic Pulmonary Fibrosis: A Systematic Review and Meta-Analysis. ERJ Open Res. 2022;8:00591–2021. doi: 10.1183/23120541.00591-2021. - DOI - PMC - PubMed
    1. Raghu G., Chen S.Y., Yeh W.S., Maroni B., Li Q., Lee Y.C., Collard H.R. Idiopathic Pulmonary Fibrosis in US Medicare Beneficiaries Aged 65 Years and Older: Incidence, Prevalence, and Survival, 2001–2011. Lancet Respir. Med. 2014;2:566–572. doi: 10.1016/S2213-2600(14)70101-8. - DOI - PubMed
    1. Kaul B., Lee J.S., Zhang N., Vittinghoff E., Sarmiento K., Collard H.R., Whooley M.A. Epidemiology of Idiopathic Pulmonary Fibrosis among U.S. Veterans, 2010–2019. Ann. Am. Thorac. Soc. 2022;19:196–203. doi: 10.1513/AnnalsATS.202103-295OC. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources

  NODES
twitter 2