Vitamin D deficiency is correlated with the increased morbidity of
chronic obstructive pulmonary disease (
COPD). However, the mechanisms underlying these effects have largely remained elusive. This study analyzed the correlations among
COPD,
vitamin D concentration, and epithelial-mesenchymal transition (EMT). Ninety-five patients with newly diagnosed
COPD and 190 age- and sex-matched healthy subjects were recruited for this research. Serum 25(
OH)D levels were detected, and pulmonary EMT
biomarkers and TGF-β/Smad signaling were evaluated. Serum 25(
OH)D level was remarkably decreased in
COPD patients compared with that in control subjects. Furthermore, serum 25(
OH)D concentration gradually decreased in
COPD patients ranging from grade 1-2 to 4. However, reduced expression of the epithelial
biomarker E-cadherin and increased expression of the mesenchymal
biomarkers vimentin and α-SMA were found in
COPD patients. Mechanistic analysis showed that pulmonary nuclear
vitamin D receptor (VDR) was decreased in patients with
COPD. In contrast, TGF-β/Smad signaling was obviously activated in
COPD patients. Furthermore, the level of serum TGF-β in
COPD patients increased in parallel with
COPD severity. Serum 25(
OH)D concentration was inversely associated with TGF-β levels in
COPD patients. In vitro experiments showed that active
vitamin D3 inhibits TGF-β-induced Smad2/3 phosphorylation in MRC-5 cells. Furthermore,
vitamin D concentration was inversely correlated with TGF-β/Smad signaling and EMT in
COPD patients, suggesting EMT as a vital mediator of
COPD development in patients with low
vitamin D concentrations.