Vasilios Tzilas1, Evangelos Bouros1, Ilianna Barbayianni2, Thodoris Karampitsakos1, Sofia Kourtidou1, Maria Ntassiou1, Ioanna Ninou2, Vassilis Aidinis2, Demosthenes Bouros1, Argyris Tzouvelekis3. 1. 1st Academic Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens, Hospital for Diseases of the Chest, "Sotiria", Athens, Greece. 2. Biomedical Sciences Research Center, "Alexander Fleming", Division of Immunology, Athens, Greece. 3. 1st Academic Department of Respiratory Medicine, Medical School, National and Kapodistrian University of Athens, Hospital for Diseases of the Chest, "Sotiria", Athens, Greece; Biomedical Sciences Research Center, "Alexander Fleming", Division of Immunology, Athens, Greece. Electronic address: argyrios.tzouvelekis@fleming.gr.
Abstract
BACKGROUND: Vitamin D (VitD) is a steroid hormone with cytoprotective and anti-inflammatory properties. Epidemiological studies have suggested a link between VitD deficiency and risk of development of chronic lung diseases. Its role in lung fibrosis is largely unknown. The aim of our study was to investigate the role of VitD in experimental and human lung fibrosis. METHODS: VitD (25-OH-D3, 2 μg/kg) was orally administered from day 3-day 13 following bleomycin-challenge, in 8-10 weeks-old C57/BL6 mice. Mouse Lung Fibroblasts (MLFs) were pre-treated with VitD (2 μM for 24 h) and then stimulated with TGFB1 (10 ng/ml). Serum samples from 93 patients with IPF and other forms of interstitial lung diseases (ILDs) were prospectively collected for VitD measurement. RESULTS: VitD administration prevented bleomycin-induced lung fibrosis, as assessed by reductions in hydroxyproline levels, mRNA levels of col1a1, col3a1 and a-SMA (1.4-, 3.1-, 2.25-, 2.5-fold, respectively) and Masson Trichrome staining compared to the untreated group and these changes were associated with restoration of the bleomycin-induced downregulation of vitamin D-receptor (Vdr) mRNA levels. Pre-treatment with VitD reduced the responsiveness of MLFs to pro-fibrotic stimuli, as indicated by significant decreases of col1a1, col3a1 and a-SMA (3.6-, 4.1- and 2.7-fold, respectively).These changes were associated with restoration of the TGFB1-induced downregulation of vitamin D-receptor (VDR) mRNA levels. VitD treatment deactivated TGFB1-induced Smad3 phosphorylation. Patients with IPF and other forms of ILDs displayed deficient VitD serum concentrations (mean VitD = 18.76 ± 8.36 vs. 18.54 ± 8.39 ng/ml, respectively, p = 0.9). VitD deficiency was correlated with baseline FVC%predicted (r = 0.47, p < 0.0001), DLCO%predicted (r = 0.6, p < 0.0001), GAP score (r = -0.4, p < 0.0001) and all-cause mortality in patients with IPF (HR: 3.7, p = 0.001). CONCLUSIONS: VitD could serve as a prognosticator and potential therapeutic target in patients with IPF. Further studies are sorely needed.
BACKGROUND:Vitamin D (VitD) is a steroid hormone with cytoprotective and anti-inflammatory properties. Epidemiological studies have suggested a link between VitD deficiency and risk of development of chronic lung diseases. Its role in lung fibrosis is largely unknown. The aim of our study was to investigate the role of VitD in experimental and humanlung fibrosis. METHODS:VitD (25-OH-D3, 2 μg/kg) was orally administered from day 3-day 13 following bleomycin-challenge, in 8-10 weeks-old C57/BL6 mice. Mouse Lung Fibroblasts (MLFs) were pre-treated with VitD (2 μM for 24 h) and then stimulated with TGFB1 (10 ng/ml). Serum samples from 93 patients with IPF and other forms of interstitial lung diseases (ILDs) were prospectively collected for VitD measurement. RESULTS:VitD administration prevented bleomycin-induced lung fibrosis, as assessed by reductions in hydroxyproline levels, mRNA levels of col1a1, col3a1 and a-SMA (1.4-, 3.1-, 2.25-, 2.5-fold, respectively) and Masson Trichrome staining compared to the untreated group and these changes were associated with restoration of the bleomycin-induced downregulation of vitamin D-receptor (Vdr) mRNA levels. Pre-treatment with VitD reduced the responsiveness of MLFs to pro-fibrotic stimuli, as indicated by significant decreases of col1a1, col3a1 and a-SMA (3.6-, 4.1- and 2.7-fold, respectively).These changes were associated with restoration of the TGFB1-induced downregulation of vitamin D-receptor (VDR) mRNA levels. VitD treatment deactivated TGFB1-induced Smad3 phosphorylation. Patients with IPF and other forms of ILDs displayed deficient VitD serum concentrations (mean VitD = 18.76 ± 8.36 vs. 18.54 ± 8.39 ng/ml, respectively, p = 0.9). VitD deficiency was correlated with baseline FVC%predicted (r = 0.47, p < 0.0001), DLCO%predicted (r = 0.6, p < 0.0001), GAP score (r = -0.4, p < 0.0001) and all-cause mortality in patients with IPF (HR: 3.7, p = 0.001). CONCLUSIONS:VitD could serve as a prognosticator and potential therapeutic target in patients with IPF. Further studies are sorely needed.
Authors: Jose Manuel Quesada-Gomez; José Lopez-Miranda; Marta Entrenas-Castillo; Antonio Casado-Díaz; Xavier Nogues Y Solans; José Luis Mansur; Roger Bouillon Journal: Nutrients Date: 2022-06-29 Impact factor: 6.706
Authors: Laura Gisbert-Ferrándiz; Jesús Cosín-Roger; Carlos Hernández; Dulce C Macias-Ceja; Dolores Ortiz-Masiá; Pedro Salvador; Juan V Esplugues; Joaquín Hinojosa; Francisco Navarro; Sara Calatayud; María D Barrachina Journal: Nutrients Date: 2020-04-01 Impact factor: 5.717