Vitamin D receptor inhibits EMT via regulation of the epithelial mitochondrial function in intestinal fibrosis

Abstract

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Diet in Intestinal Fibrosis: A Double-Edged Sword

“…Johnson et al have demonstrated that CARD-024, a vitamin D analogue was able to reduce ECM-associated markers in TGF-β-stimulated or stiffness-induced colonic fibroblasts [ 60 ]. In addition, down-regulation of colon VDR is observed in chronic CD patients and also in mice with chronic DSS-induced colitis and fibrosis [ 61 ]. VDR is also reduced in fibroblasts from CD patients [ 62 ].…”

“…Mitochondrial dysfunction has been described in patients with IBD and genetic deletion of prohibitin 1, a key protein of the inner mitochondrial membrane decreased in IBD, which can provoke ileitis in mice [ 63 ]. VDR is also involved in mitochondrial dysfunction [ 61 ] and its specific role in intestinal fibrosis has been recently demonstrated [ 61 ]. The authors of this elegant study first demonstrated that VDR expression was lower in intestinal stenotic areas in CD patients [ 61 ].…”

“…VDR is also involved in mitochondrial dysfunction [ 61 ] and its specific role in intestinal fibrosis has been recently demonstrated [ 61 ]. The authors of this elegant study first demonstrated that VDR expression was lower in intestinal stenotic areas in CD patients [ 61 ]. They then induced colitis-induced fibrosis by TNBS or DSS in mice with intestine-specific VDR deletion and they found that VDR deletion exacerbated intestinal fibrosis in both models.…”

“…They then induced colitis-induced fibrosis by TNBS or DSS in mice with intestine-specific VDR deletion and they found that VDR deletion exacerbated intestinal fibrosis in both models. To decipher the mechanism underlying these anti-fibrosis effects, they used VDR invalidation in colonic fibroblasts, leading to their activation [ 61 ]. VDR invalidation also induced mitochondrial dysfunction mediated epithelial integrity.…”

Tanshinone IIA attenuates high glucose-induced epithelial-to-mesenchymal transition in HK-2 cells through VDR/Wnt/β-catenin signaling pathway

“…Previous studies have suggested that the activation of the Wnt/β-catenin signaling pathway is highly involved in the process of various organ fibrosis [3] such as renal [4], liver [5], peritoneal [6], and dermal fibrosis [7]. Studies also found that the upregulation of the vitamin D receptor (VDR) might contribute to the alleviation of organ fibrosis [8]. Moreover, VDR gene can regulate the expression of many genes, and the analysis of Targetscan database by Cong [9] suggested that Wnt gene and βcatenin gene may be potential targets of VDR protein.…”