OBJECTIVETo review the advances of studies on vitamin D receptor and its role in the pathogenesis of diabetic nephropathy.

DATA SOURCESA comprehensive search of the PubMed literatures without restriction on the publication date was carried out using keywords such as vitamin D receptor and diabetic nephropathy.

STUDY SELECTIONArticles related to vitamin D receptor and diabetic nephropathy were selected and carefully analyzed.

RESULTSThe ligands as well as construction and tissue distribution of vitamin D receptor were summarized. Pathogenesis of diabetic nephropathy was analyzed. The mechanisms underlying the renoprotective role of vitamin D receptor including inhibition of renin-angiotensin system, anti-inflammation, anti-fibrosis and the reduction of proteinuria were reviewed. Mounting evidences from animal and clinical studies have suggested that vitamin D therapy has beneficial effects on the renal systems and the underlying renoprotective mechanisms of the vitamin D receptor-mediated signaling pathways is a hot research topic.

CONCLUSIONOur study suggests that vitamin D receptor has a great potential for preventing the progression of diabetic nephropathy via multiple mechanisms.

Animals ; Diabetic Nephropathies ; metabolism ; Humans ; Proteinuria ; metabolism ; Receptors, Calcitriol ; metabolism ; Renin-Angiotensin System ; physiology

Vitamin D plays an important role in mineral and bone homeostasis, immune responses, cardiovascular function and keratinocyte proliferation and differentiation. Vitamin D performs most of its functions by binding to vitamin D receptors (VDR), which interact with other intracellular signaling pathways to regulate bone metabolism, inflammation, immunity, cell cycle progression and apoptosis. Autophagy is a basic stress response in yeast, plants and mammals, and plays a critical role in maintaining optimal functional states at the level of cells and organs. Vitamin D/VDR plays an anti-infection role via inducing and regulating autophagy.
Animals ; Autophagy ; Humans ; Inflammation ; Mammals/metabolism* ; Receptors, Calcitriol/metabolism* ; Vitamin D/physiology* ; Vitamins

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*

OBJECTIVE: To identify the miRNAs targeting vitamin D receptor (VDR) gene and their effect on parathyroid hormone (PTH) secretion in secondary hyperparathyroidism. METHODS: Primary parathyroid cells with secondary hyperparathyroidism were isolated by collagenase digestion and cultured. The miRNAs targeting VDR were screened by bioinformatics methods and full transcriptome sequencing, and dual-luciferase reporter assay was used to verify the targeting relationship between VDR and the screened miRNA. The effects of overexpression or inhibition of the candidate miRNA on VDR mRNA and protein expressions and PTH secretion were evaluated using qRT-PCR and Western blotting. The expression levels of the candidate miRNAs and VDR mRNA in clinical specimens of parathyroid tissues were verified by qRT-PCR, and the expression of VDR protein was detected by immunohistochemistry. RESULTS: We successfully isolated primary parathyroid cells. Dual-luciferase reporter assay verified the targeting relationship of hsa-miR-149-5p, hsa-miR-221-5p, hsa-miR-222-3p, hsa-miR-29a-5p, hsa-miR-301a-5p, hsa-miR-873-5p, hsa-miR-93-3p with VDR, and among them, the overexpression of hsa-miR-149-5p and hsa-miR-301a-5p significantly increased PTH secretion in the parathyroid cells. In patients with secondary hyperparathyroidism, hsa-miR-149-5p was highly expressed in the parathyroid tissues (P=0.046), where the expressions of VDR mRNA (P=0.0267) and protein were both decreased. CONCLUSION The two miRNAs, hsa-miR-149-5p and hsa-miR-301a-5p, may promote the secretion of PTH in patients with secondary hyperparathyroidism by down-regulating the expression of VDR gene.
Humans ; Hyperparathyroidism, Secondary/genetics* ; MicroRNAs/metabolism* ; Parathyroid Hormone ; RNA, Messenger ; Receptors, Calcitriol/genetics*

OBJECTIVE: To investigate the expression and concentration of lipopolysaccharide (LPS) and matrix metalloproteinase-9 (MMP-9) in middle ear cholesteatoma and discuss their relations. METHOD: Twenty-nine cases of middle ear cholesteatoma tissue, 18 cases of external auditory canal tissue were detected by limulus amebocyte lysate assay (LAL-assay), and expression of MMP-9 protein in formalin-fixed, paraffin-embedded tissues was detected by immunohistochemical method. RESULT: The concentrations of LPS in cholesteatoma were higher than that in external auditory canal tissues. In group of cholesteatoma: M = 0.739 0, IQR = 0.6203, and in group of external auditory canal tissues: M = -0.2538, IQR = 1.1692 (P < 0.01). In cholesteatoma groups, in extensive type: M = 0.8403, IQR = 0.5254; in localized type: M = 0.4048, IQR = 0.6139, the concentrations of LPS were higher in extensive cholesteatoma in comparison with localized cholesteatoma (P < 00.05). In cholesteatoma epithelium samples, MMP-9 were 79.3%. Compared with external auditory canal epithelium, the expression of MMP-9 was higher in middle ear cholesteatoma epithelium (P < 0.05). There was no significant difference in the expression of MMP-9 between two types of cholesteatoma epithelium (P > 0.05). LPS, MMP-9 weren't significantly correlated by Spearman test. CONCLUSION LPS was responsible for middle ear cholesteatoma and its related bone erosion. MMP-9 was related to the development of middle ear cholesteatoma. There's no correlation between LPS and MMP-9.
Adult ; Cholesteatoma, Middle Ear ; metabolism ; pathology ; Female ; Humans ; Lipopolysaccharides ; metabolism ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Receptors, Calcitriol ; metabolism

To evaluate the association of Toll-like receptors (TLRs), antimicrobial peptides (AMPs) and vitamin D receptors (VDRs) in psoriasis, lesional (PP) and perilesional skin (PN) from psoriasis, atopic dermatitis (AD) patients and healthy controls (NN) were studied by immunohistochemistry. Compared with PN, AD and NN skin, dysregulated expression of TLRs, AMPs and VDR was detected in PP skin. Noteworthy, our results showed altered correlation between TLR2 and VDR expression in PP and PN skin. Human beta defensin 2 (HBD2) and cathelicidin (LL-37) expressions in the PP skin were higher in serum vitamin D sufficient (VDS) groups than serum vitamin D deficient (VDD) groups. Negative correlation was found between TLR2 and VDR expression in the PP skin of VDD groups. However, positive correlation was noted in the PP skin of VDS groups. Based on the present results, therapies targeting the activity of TLRs, AMPs and vitamin D, including modulation of the TLR-VDR pathways, might provide new therapeutic approaches to the psoriasis and other inflammatory skin diseases.
Anti-Infective Agents/*metabolism ; Antimicrobial Cationic Peptides/*metabolism ; Female ; Humans ; Male ; Psoriasis/*metabolism ; Receptors, Calcitriol/metabolism ; Toll-Like Receptors/*metabolism ; Vitamin D/*blood ; beta-Defensins/metabolism

Over the past decade, there has been increasing attention on the interaction between microbiota and bile acid metabolism. Bile acids are not only involved in the metabolism of nutrients, but are also important in signal transduction for the regulation of host physiological activities. Microbial-regulated bile acid metabolism has been proven to affect many diseases, but there have not been many studies of disease regulation by microbial receptor signaling pathways. This review considers findings of recent research on the core roles of farnesoid X receptor (FXR), G protein-coupled bile acid receptor (TGR5), and vitamin D receptor (VDR) signaling pathways in microbial-host interactions in health and disease. Studying the relationship between these pathways can help us understand the pathogenesis of human diseases, and lead to new solutions for their treatments.
Bile Acids and Salts/metabolism* ; Gastrointestinal Microbiome ; Humans ; Inflammation/metabolism* ; Metabolic Syndrome/metabolism* ; Receptors, Calcitriol/physiology* ; Receptors, Cytoplasmic and Nuclear/physiology* ; Receptors, G-Protein-Coupled/physiology* ; Signal Transduction/physiology*

OBJECTIVETo evaluate the effect of 25-hydroxyvitamin D(3) on the expression and distribution of vitamin D receptor in normal human bronchial epithelial cells.

METHODSMTT assay was used to assess the viability of human airway epithelial cell line 16HBE following a 24-h exposure to different concentrations of 25-hydroxyvitamin D(3). Real-time quantitative PCR, Western blotting, and immunofluorescence assay were used to observe the expression and distribution of vitamin D receptor in the cells following the exposure.

RESULTSCompared with the control cells, 16HBE cells exposed to different concentrations of 25-hydroxyvitamin D(3) exhibited no significantly increase in the expression or distribution of vitamin D receptor.

CONCLUSIONThe influence of 25-hydroxyvitamin D(3) on bronchial epithelial cells might be independent of the expression and translocation of vitamin D receptor.

Bronchi ; cytology ; Calcifediol ; pharmacology ; Cell Line ; Epithelial Cells ; cytology ; metabolism ; Humans ; RNA, Messenger ; genetics ; metabolism ; Receptors, Calcitriol ; genetics ; metabolism

PURPOSE: It is known that secondary hyperparathyroidism in end stage renal disease (ESRD) patients is associated with vitamin D receptor (VDR) gene polymorphism, but there is no consensus on its genotype. There is lack of data in Ca, P, calcitriol and VDR polymorphism. METHODS: We measured serum Ca, P, alkaline phosphatase, parathyroid hormone (PTH), and 1,25 (OH)2D3 of the 53 hemodialysis patients. The genotypes of VDR were classified BB, Bb, bb according to restriction patterns in PCR of the patients' DNA using Bsm I restriction enzyme. RESULTS: The patients with BB, Bb, bb type were 0 (0%), 15 (28.3%), 38 (71.7%) respectively. Serum PTH levels were 70.0+/-63.3 pg/mL and 146.9+/-184.9 pg/mL in Bb, bb type respectively, and showed significant statistical difference (p<0.05). Serum 1,25 (OH)2D3 levels were 7.68+/-3.41 pg/mL and 6.59+/-2.67 pg/mL in Bb and bb genotype respectively without statistical significance. And there was no significant statistical differences among the serum levels of calcium, phosphorus, alkaline phosphatase. CONCLUSION: Vitamin D receptor gene polymorphism is associated with secondary hyperparathyroidism in hemodialysis patients, and the b allelle is suggestive of poorer bone mineral metabolism.
Alkaline Phosphatase ; Calcitriol ; Calcium ; Consensus ; DNA ; Genotype ; Humans ; Hyperparathyroidism ; Hyperparathyroidism, Secondary* ; Kidney Failure, Chronic ; Metabolism ; Parathyroid Hormone ; Phosphorus ; Polymerase Chain Reaction ; Receptors, Calcitriol* ; Renal Dialysis* ; Vitamin D* ; Vitamins*

OBJECTIVETo study the effects of 1, 25-dihydroxyvitamin D(3) (VD(3)) on the expression of vitamin D receptor (VDR), receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) in human periodontal ligament cells (hPDLC) populations and to analyze the potential mechanisms.

METHODSTwelve hPDLC populations were primarily established from 12 donors individually. Two samples of each hPDLC population of passage three were treated respectively with 10(-8) mol/L VD(3) (V D(3) group) or 0.1% absolute ethyl alcohol as controls (control group). Six days later, the mRNA expression levels of VDR, RANKL and OPG in the samples were determined with real-time quantitative RT-PCR. The DNA base sequences upstream to the transcription start site of RANKL gene were also analyzed.

RESULTSCompared with the control group, the mRNA expression level of VDR increased significantly in the VD(3) group (P = 0.003), averagely (3.04 +/- 1.06) times of that in the control group; the mRNA expression level of RANKL was also up-regulated by VD(3) (P = 0.001), 9.82 (0.75-119.18) times of that in the control group; the OPG expression level was (94.48 +/- 39.15)% of the controls (P = 0.136); OPG/RANKL ratio was down-regulated in the VD(3) group to averagely 10.36% (1.01%-138.00%) of the controls (P = 0.003). No mutation was found in the DNA fragments upstream to the transcription start site in the RANKL gene and the genotypes of the polymorphism at -1832 (rs7984870, C/G) were not shown to be significantly related to the RANKL mRNA expression level.

CONCLUSIONSIn hPDLC, VD(3) can significantly increase the mRNA expression level of VDR; VD(3) can increase RANKL mRNA expression level to decrease OPG/RANKL ratio, but it has little effect on OPG mRNA expression. The big differences of the RANKL mRNA regulation in response to VD(3) treatment among hPDLC populations may not be associated with the DNA sequences upstream to the transcription start site in the RANKL gene.

Adolescent ; Calcitriol ; pharmacology ; Cells, Cultured ; Down-Regulation ; Female ; Humans ; Male ; Osteoprotegerin ; metabolism ; Periodontal Ligament ; drug effects ; metabolism ; RANK Ligand ; metabolism ; Receptor Activator of Nuclear Factor-kappa B ; metabolism ; Receptors, Calcitriol ; metabolism ; Up-Regulation ; Young Adult