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. 2022 Sep 21;14(19):3908. doi: 10.3390/nu14193908

Table 1.

Summary of the pre-clinical study selected. Abbreviations: vit D, vitamin D; SSc, systemic sclerosis; VDR, vitamin D receptors; k/o, knock out; TGF, transforming growth factor; Th, T helper; Treg, regulatory T cells; IL, interleukin; RORγ, Retinoic-acid-receptor-related orphan nuclear receptor gamma; HOCl, hypochlorous acid; MMP, metalloproteinase; TIMP, tissue inhibitor of metalloproteinase 1.

Authors Journal and Year Methods Endpoint Main Findings
Slominski et al. [27] J. Clin. Endocrinol. Metab., 2013 Human dermal fibroblasts from SSc and healthy controls in vitro; murine models of bleomycin-induced skin fibrosis Test the potential antifibrogenic activity of vit D analog The noncalcemic analogs of vit D, 20(OH)D3, and 20,23(OH)2D3 inhibited TGF-β 1-induced collagen and hyaluronan synthesis similarly to 1,25(OH)2D3 in cultured human fibroblasts
20(OH)D3 suppressed fibrogenesis in bleomycin-model mice as demonstrated by skin biopsies
Usategui et al. [28] Arch. Dermatol. Res., 2014 Bleomycin-induced fibrosis mouse model of scleroderma Prove the potential of topical vit D to treat skin fibrosis In topical calcipotriol-treated mice, the dermal collagen area and the dermal thickness were significantly reduced.
Zerr et al. [29] Ann. Rheum. Dis., 2015 Fibroblasts from SSc patients and healthy controls; induced bleomycin skin fibrosis in VDR k/o mice Role of VDR signaling in SSc fibrosis VDR expression (mRNA and protein) is reduced in SSc fibroblasts and the murine model of skin fibrosis in a TGFbeta dependent
manner.
Vit D analog paricalcitol, through VDR signaling, inhibited TGF-beta signaling 
and ameliorated experimental fibrosis
Terao et al. [30] Dermatoendocrinology, 2015 Normal human fibroblasts cultures; fibroblasts from a bleomycin-induced scleroderma mouse model Effect of vit D analog on Th2 cytokine-induced periostin production by fibroblasts Vit D analog maxacalcitol decreased the density of collagen bundles and periostin expression in the murine model; moreover, it decreased the expression of periostin in dermal fibroblasts, and the Th2 cytokine and TGFbeta-induced expression of periostin and Col1A1.
Di Liberto et al. [31] Clin. Exp. Rheumatol., 2019 Treg isolated from blood and sera samples of SSc and controls Effect of vit D supplementation on Treg in SSc patients Tregs from SSc patients taking vit D increased in percentages; Tregs obtained from SSc patients failed to suppress T cell proliferation even after stimulation with vit D. However, vit D induced the production of IL-10
Janjetovic et al. [32] Endocrinology, 2021 Bleomycin-Mouse model and murine fibroblasts Effect of 20(OH)D3 on fibroblasts and role of RORγ 20(OH)D3 inhibited proliferation of RORγ+/+ fibroblasts and TGbeta-induced collagen synthesis.
Ge et al. [33] Biochem. Biophys. Res. Commun., 2022 VDR knockout mice; HOCl-induced mice model of scleroderma Explore the mechanism of VDR in SSc VDR deficiency in keratinocytes promoted fibrosis; ablation of VDR in epidermidis upregulated expression of pro-inflammatory cytokines and aggravated fibrosis.
Brown Lobbins et al. [34] Int. J. Mol. Sci., 2022 Skin biopsy from a bleomycin-induced scleroderma mouse model Vit D-analog capacity of suppression the fibrosis in a murine model 17,20S(OH)2pD suppressed total collagen content, prevented the development of increased dermal thickness in a murine model, and suppressed TGF-β collagene synthesis in the murine model
Brown Lobbins et al. [35] Int. J. Mol. Sci., 2022 Dermal cultured fibroblasts from SSc patients and controls Vit D-analog capacity of suppression of collagen production by fibroblasts 17,20S(OH)2pD increased MMP-1 in dermal fibroblasts and decreased TIMP-1 protein synthesis and modulated mediators of fibrosis in vitro.