Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms that control fibroproliferation and matrix deposition in lung fibrosis remain unclear. We speculate that vitamin D deficiency may contribute to pulmonary fibrosis since vitamin D deficiency has been implicated in several diseases. First, we confirmed the presence of vitamin D receptors (VDRs) in cultured NIH/3T3 and lung fibroblasts. Fibroblasts transfected with a vitamin D response element-reporter construct and exposed to the active vitamin D metabolite, 1,25(OH)(2)D(3), showed increased promoter activity indicating VDR functionality in these cells. Testing the effects of 1,25(OH)(2)D(3) on fibroblasts treated with transforming growth factor beta1 (TGFbeta1), considered a driver of many fibrotic disorders, we found that 1,25(OH)(2)D(3) inhibited TGFbeta1-induced fibroblast proliferation in a dose-dependent fashion. 1,25(OH)(2)D(3) also inhibited TGFbeta1 stimulation of alpha-smooth muscle actin expression and polymerization and prevented the upregulation of fibronectin and collagen in TGFbeta1-treated fibroblasts. Finally, we examined how 1,25(OH)(2)D(3) affects epithelial-mesenchymal transformation of lung epithelial cells upon exposure to TGFbeta1. We showed that the TGFbeta1-induced upregulation of mesenchymal cell markers and abnormal expression of epithelial cell markers were blunted by 1,25(OH)(2)D(3). These observations suggest that under TGFbeta1 stimulation, 1,25(OH)(2)D(3) inhibits the pro-fibrotic phenotype of lung fibroblasts and epithelial cells.
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PMID:Vitamin D inhibition of pro-fibrotic effects of transforming growth factor beta1 in lung fibroblasts and epithelial cells. 1993 90

Pulmonary fibrosis, which influences lung function and exacerbates a patient's condition, is the ultimate stage of many lung diseases. Vitamin D deficiency is associated with pulmonary fibrosis and impaired lung function, but the underlying mechanism has not yet been fully elucidated. Moreover, vitamin D deficiency may cause over-activation of the renin-angiotensin system (RAS), which aggravates extracellular matrix (ECM) deposition and lung fibrosis. This study aims to investigate the effect of chronic vitamin D deficiency on lung fibrosis in otherwise healthy mice and to explore the role of RAS in this process. Mice were depleted of vitamin D through diet control and were compared with healthy subjects. Chronic vitamin D deficiency destructs lung structures, impairs lung development and stimulates ECM deposition. RAS components are also found to increase. These effects seem to worsen with prolonged vitamin D deficiency. By giving RAS blockers, these changes can be largely rescued. However, a smooth muscle relaxant whose regulatory effect on blood pressure is independent of RAS does not show similar effects. This study demonstrated that chronic vitamin D deficiency may induce RAS activation, which subsequently stimulates the expression of profibrotic factors and activates the fibrotic cascade. This profibrotic effect of RAS is independent of elevated blood pressure.
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PMID:Chronic vitamin D deficiency induces lung fibrosis through activation of the renin-angiotensin system. 2860 92

Pulmonary fibrosis is a serious interstitial disease characterized by initial diffuse alveolar inflammation, fibroblast proliferation, ECM accumulation, and the destruction of normal pulmonary tissues, whose etiology remains unknown and therapeutic options remain limited. The prevalence of Vitamin D deficiency is increasing and has been linked to pulmonary fibrosis. In recent years, many studies focused on the mechanistic pathway of Vitamin D in the prevention of fibrosis. This review highlights the current evidence on the molecular mechanisms of Vitamin D in pulmonary fibrosis. We want to provide new clues to the clinical management of pulmonary fibrosis.
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PMID:Vitamin D and pulmonary fibrosis: a review of molecular mechanisms. 3193 61