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2015 ; 36
(4
): 967-74
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1?,25-Dihydroxyvitamin D3 prevents the differentiation of human lung fibroblasts
via microRNA-27b targeting the vitamin D receptor
#MMPMID26311239
Li F
; Zhang A
; Shi Y
; Ma Y
; Du Y
Int J Mol Med
2015[Oct]; 36
(4
): 967-74
PMID26311239
show ga
Pulmonary fibroblasts have key roles in the formation and maintenance of lung
structure and function, and are involved in tissue repair and remodeling.
Transforming growth factor??1 (TGF??1) induces differentiation of fibroblasts
into myofibroblasts, the key effector cells in fibrotic states, which are
characterized by the expression of ??smooth muscle actin (??SMA) markers.
1?,25?Dihydroxyvitamin D3 [1,25(OH)2D3] has been implicated in regulating
differentiation, and the vitamin D receptor (VDR) may be a regulator of TGF??
signaling. In addition, there is presently only limited information regarding
microRNA (miRNA) regulation of lung fibroblast differentiation. To determine the
role of 1,25(OH)2D3 in regulating the differentiation of fibroblasts induced by
TGF??1 and the functional importance of miR?27b, cell culture systems, cell
transfection and the 3' untranslated region (3'UTR) luciferase assay were
employed. 1,25(OH)2D3 inhibited differentiation and downregulated miR?27b
expression in human lung fibroblasts induced by TGF??1. In addition, human lung
fibroblasts were transfected with miR?27b mimic or miR?27b inhibitor, and
demonstrated that the overexpression of miR?27b decreased the VDR protein
expression and increased the expression of ??SMA, while reducing levels of
miR?27b had opposing effects. Finally, the luciferase reporter assays were
performed to confirm that miR?27b directly targeted VDR 3'UTR. Taken together,
these results suggest that 1,25(OH)2D3 inhibits lung fibroblast differentiation
induced by TGF??1 via miR?27b targeting VDR 3'UTR, which may be used as a novel
treatment strategy in differentiation pathways.