Abstract
Patients with pulmonary fibrosis often have low vitamin D levels, the effects of which are largely unknown. We here report that early vitamin D supplementation significantly reduced the severity of pulmonary fibrosis and inflammatory cell accumulationin in the bleomycin-induced pulmonary fibrosis mouse model on supplementary days 14, 21 and 28 (P < 0.001). Vitamin D supplementation also prevented some ultrastructural changes in response to bleomycin administration, including basement membrane thickening, interstitial fibrin deposition and microvilli flattening or disappearance on days 14, 21 and 28, and lamellar body swelling or vacuolation on days 21 and 28. The bleomycin group had rising hydroxyproline level on days 14, 21 and 28, whereas the vitamin D treatment group showed consistently lower hydroxyproline level but still higher than that of the control group (P < 0.001). Our immunohistochemistry and densitometry analyses showed less staining for α-smooth muscle actin, a myofibroblast marker, in the vitamin D group compared to the bleomycin group (P < 0.001). Thus, vitamin D treatment could prevent bleomycin-induced pulmonary fibrosis by delaying or suppressing ultrastructural changes, as well as attenuating hydroxyproline accumulation and inhibiting myofibroblastic proliferation. These data further our understanding of the roles of vitamin D in pulmonary fibrogenesis and in the treatment of pulmonary fibrosis.
Highlights
Mortality due to idiopathic pulmonary fibrosis (IPF) has increased over the past two decades to rates of 61.2 deaths per 1,000,000 men and 54.5 deaths per 1,000,000 women per year in the USA1
We first observed the histological changes in groups of control, bleomycin, bleomycin + vitamin D, and vitamin D using H&E staining (Fig. 1), Masson trichrome staining (Fig. 2) and Ashcroft’s fibrosis scoring system (Table 1)
We sought to explore the effects of vitamin D treatment on these ultrastructural changes and organellar injuries
Summary
Mortality due to idiopathic pulmonary fibrosis (IPF) has increased over the past two decades to rates of 61.2 deaths per 1,000,000 men and 54.5 deaths per 1,000,000 women per year in the USA1. A histological pattern typical of interstitial pneumonia is one of the diagnostic criteria for IPF, including increased interstitial fibrosis (scarring and honeycomb changes) and the presence of myofibroblasts and fibroblasts in fibroblastic foci[1,2,3]. Vitamin D or its analogs have been associated with fibrosis regulation or found to be useful for treating fibrosis in multiple organs, such as the bone, kidney and liver, but its possible effect on pulmonary fibrosis has not been evaluated. The roles of vitamin D in the pathogenesis and treatment of IPF are largely unknown. We investigated the effects of vitamin D treatment on bleomycin-induced pulmonary fibrosis in mice, with a focus on the roles of vitamin D in its ultrastructural and cellular changes
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