The Role of Vitamin D and Its Receptor Signaling in Diabetic Nephropathy and the Current Status of Research: A Literature Review
Keywords:
Diabetic nephropathy, vitamin D, vitamin D receptor, kidney injury, bibliometricsAbstract
Diabetic kidney disease (DKD) is one of the common and serious complications of diabetes mellitus, with a complex pathogenesis and a lack of ideal treatment options in clinical practice. In recent years, the protective role of vitamin D and its receptor signaling pathway in DKD has garnered widespread attention. Vitamin D plays an important role in the onset and progression of DKD by participating in the regulation of insulin secretion, inhibiting inflammatory responses, attenuating podocyte injury, modulating the renin-angiotensin system (RAS), and inhibiting renal interstitial fibrosis through its receptor (VDR). Studies on the use of vitamin D and its receptors in DKD have increased gradually in recent years, with a focus on the development of vitamin D analogs and the clinical application of VDR activators. This study reviewed the mechanisms of vitamin D and its receptor in diabetic nephropathy, as well as the potential for therapeutic applications and associated adverse effects. It also analyzed current research hotspots and development trends based on bibliometrics. Future research should focus on further optimizing vitamin D-based therapeutic strategies to achieve better clinical efficacy and safety.References
Abdel Moneim LM, Helmy MW, El-Abhar HS. Co-targeting of endothelin-(A) and vitamin D receptors: a novel strategy to ameliorate cisplatin-induced nephrotoxicity. Pharmacol Rep. 2019;71(5):917-25.
Karra P, Winn M, Pauleck S, et al. Metabolic dysfunction and obesity-related cancer: beyond obesity and metabolic syndrome. Obesity (Silver Spring, Md). 2022;30(7):1323-34.
Ritz E, Rychlík I, Locatelli F, Halimi S. End-stage renal failure in type 2 diabetes: a medical catastrophe of worldwide dimensions. Am J Kidney Dis. 1999;34(5):795-808.
Jung CY, Yoo TH. Pathophysiologic mechanisms and potential biomarkers in diabetic kidney disease. Diabetes Metab J. 2022;46(2):181-97.
Scilletta S, Di Marco M, Miano N, et al. Update on diabetic kidney disease (DKD): Focus on non-albuminuric DKD and cardiovascular risk. Biomolecules. 2023;13(5).
Liu WJ, Huang WF, Ye L, et al. The activity and role of autophagy in the pathogenesis of diabetic nephropathy. Eur Rev Med Pharmacol Sci. 2018;22(10):3182-9.
Kitada M, Ogura Y, Monno I, Koya D. Regulating autophagy as a therapeutic target for diabetic nephropathy. Curr Diab Rep. 2017;17(7):53.
Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiological Reviews. 2016;96(1):365-408.
Bouillon R, Marcocci C, Carmeliet G, et al. Skeletal and extraskeletal actions of vitamin D: Current evidence and outstanding questions. Endocrine Reviews. 2019;40(4):1109-51.
Galuška D, Pácal L, Kaňková K. Pathophysiological implication of vitamin D in diabetic kidney disease. Kidney & blood pressure research. 2021;46(2):152-61.
Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006;92(1):4-8.
Andress DL. Vitamin D in chronic kidney disease: a systemic role for selective vitamin D receptor activation. Kidney International. 2006;69(1):33- 43.
Yang S, Li A, Wang J, et al. Vitamin D receptor: a novel therapeutic target for kidney diseases. Curr Med Chem. 2018;25(27):3256-71.
Pike JW, Meyer MB, Lee SM, Onal M, Benkusky NA. The vitamin D receptor: contemporary genomic approaches reveal new basic and translational insights. J Clin Invest. 2017;127(4):1146-54.
Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol. 2020;16(7):377-90.
Lei M, Liu Z, Guo J. The emerging role of vitamin D and vitamin D receptor in diabetic nephropathy. Biomed Res Int. 2020;2020:4137268.
Wang H, Yu X, Liu D, et al. VDR activation attenuates renal tubular epithelial cell ferroptosis by regulating Nrf2/HO-1 signaling pathway in diabetic nephropathy. Adv Sci (Weinh). 2024;11(10):e2305563.
Tsur A, Feldman BS, Feldhammer I, Hoshen MB, Leibowitz G, Balicer RD. Decreased serum concentrations of 25-hydroxycholecalciferol are associated with an increased risk of progression to impaired fasting glucose and diabetes. Diabetes Care. 2013;36(5):1361-7.
Wang Y, Yang S, Zhou Q, Zhang H, Yi B. Effects of vitamin D supplementation on renal function, inflammation and glycemic control in patients with diabetic nephropathy: A systematic review and meta-analysis. Kidney & blood pressure research. 2019;44(1):72-87.
Huang HY, Lin TW, Hong ZX, Lim LM. Vitamin D and diabetic kidney disease. Int J Mol Sci. 2023;24(4).
Taderegew MM, Woldeamanuel GG, Wondie A, Getaway A, Abegaz AN, Adane F. Vitamin D deficiency and its associated factors among patients with type 2 diabetes mellitus: a systematic review and meta-analysis. BMJ open. 2023;13(10):e075607.
Kadowaki S, Norman AW. Dietary vitamin D is essential for normal insulin secretion from the perfused rat pancreas. J Clin Invest. 1984;73(3):759-66.
Karnchanasorn R, Ou HY, Chiu KC. Plasma 25-hydroxyvitamin D levels are favorably associated with β-cell function. Pancreas. 2012;41(6):863-8.
Bornstedt ME, Gjerlaugsen N, Pepaj M, Bredahl MKL, Thorsby PM. Vitamin D increases glucose stimulated insulin secretion by insulin producing beta cells (INS1E). Int J Endocrinol Metab. 2019;17(1):e74255.
Wimalawansa SJ. Associations of vitamin D with insulin resistance, obesity, type 2 diabetes, and metabolic syndrome. J Steroid Biochem Mol Biol. 2018;175:177-89.
Hosseini ES, Kashani HH, Nikzad H, et al. Diabetic hemodialysis: Vitamin D supplementation and its related signaling pathways involved in insulin and lipid metabolism. Curr Mol Med. 2019;19(8):570-8.
Lemieux P, Weisnagel SJ, Caron AZ, et al. Effects of 6-month vitamin D supplementation on insulin sensitivity and secretion: a randomized, placebo-controlled trial. Eur J Endocrinol. 2019;181(3):287-99.
Samsu N. Diabetic nephropathy: Challenges in pathogenesis, diagnosis, and treatment. Biomed Res Int. 2021;2021:1497449.
Navarro JF, Mora C. Role of inflammation in diabetic complications. Nephrol Dial Transplant. 2005;20(12):2601-4.
Royall JA, Berkow RL, Beckman JS, Cunningham MK, Matalon S, Freeman BA. Tumor necrosis factor and interleukin 1 alpha increase vascular endothelial permeability. Am J Physiol. 1989;257(6 Pt 1): L399-410.
Melcion C, Lachman L, Killen PD, Morel-Maroger L, Striker GE. Mesangial cells, the effect of monocyte products on proliferation and matrix synthesis. Transplant Proc. 1982;14(3):559-64.
Dalla Vestra M, Mussap M, Gallina P, et al. Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. J Am Soc Nephrol. 2005;16 Suppl 1:S78-82.
Hirano T, Akira S, Taga T, Kishimoto T. Biological and clinical aspects of interleukin 6. Immunol Today. 1990;11(12):443-9.
Donate-Correa J, Ferri CM, Sánchez-Quintana F, et al. Inflammatory cytokines in diabetic kidney disease: pathophysiologic and therapeutic implications. Front Med (Lausanne). 2020;7:628289.
Lee S, Huen S, Nishio H, et al. Distinct macrophage phenotypes contribute to kidney injury and repair. j Am Soc Nephrol. 2011;22(2):317-26.
Hu X, Liu W, Yan Y, et al. Vitamin D protects against diabetic nephropathy: Evidence-based effectiveness and mechanism. Eur J Pharmacol. 2019;845:91-8.
Zhang X, Zhao Y, Zhu X, et al. Active vitamin D regulates macrophage M1/M2 phenotypes via the STAT-1-TREM-1 pathway in diabetic nephropathy. j Cell Physiol. 2019;234(5):6917-26.
Zhang XL, Guo YF, Song ZX, Zhou M. Vitamin D prevents podocyte injury via regulation of macrophage M1/M2 phenotype in diabetic nephropathy rats. Endocrinology. 2014;155(12):4939-50.
Fu H, Liu S, Bastacky SI, Wang X, Tian XJ, Zhou D. Diabetic kidney diseases revisited: a new perspective for a new era. Mol Metab. 2019;30:250-63.
Xu L, Zhang P, Guan H, et al. Vitamin D and its receptor regulate lipopolysaccharide-induced transforming growth factor-β, angiotensinogen expression, and podocyte apoptosis through the nuclear factor-κB pathway. J Diabetes Investig. 2016;7(5):680-8.
Deb DK, Wang Y, Zhang Z, et al. The molecular mechanism underlying 1,25-dihydroxyvitamin D regulation of nephrin gene expression. J Biol Chem. 2011;286(37):32011-7.
Trohatou O, Tsilibary EF, Charonis A, Iatrou C, Drossopoulou G. Vitamin D3 ameliorates podocyte injury through the nephrin signaling pathway. j Cell Mol Med. 2017;21(10):2599-609.
Shi L, Xiao C, Zhang Y, et al. Vitamin D/vitamin D receptor/Atg16L1 axis maintains podocyte autophagy and survival in diabetic kidney disease. Ren Fail. 2022;44(1):694-705.
Gnudi L, Coward RJM, Long DA. Diabetic nephropathy: Perspective on novel molecular mechanisms. Trends in Endocrinology and Metabolism: TEM. 2016. 27(11):820-30.
Lin L, Phillips WE, Manning RD. Intrarenal Angiotensin ii is associated with inflammation, renal damage, and dysfunction in dahl salt-sensitive hypertension. J Am Soc Hypertens. 2009;3(5):306-14.
Riera M, Anguiano L, Clotet S, et al. Paricalcitol modulates ACE2 shedding and renal ADAM17 in NOD mice beyond proteinuria. Am J Physiol Renal Physiol. 2016;310(6):F534-46.
Eltablawy N, Ashour H, Rashed LA, Hamza WM. Vitamin D protection from rat diabetic nephropathy is partly mediated through Klotho expression and renin-angiotensin inhibition. Arch Physiol Biochem. 2018;124(5):461-7.
fine LG, Norman JT. Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics. Kidney international. 2008;74(7):867-72.
Chen H, Zhang H, Li AM, et al. VDR regulates mitochondrial function as a protective mechanism against renal tubular cell injury in diabetic rats. Redox Biol. 2024;70:103062.
Zhang Z, Sun L, Wang Y, et al. Renoprotective role of the vitamin D receptor in diabetic nephropathy. Kidney international. 2008;73(2):163-71.
Manucha W, Juncos LI. The protective role of vitamin D on the heart and the kidney. Ther Adv Cardiovasc Dis. 2017;11(1):12-9.
Zhang Y, Kong J, Deb DK, Chang A, Li YC. Vitamin D receptor attenuates renal fibrosis by suppressing the renin-angiotensin system. J Am Soc Nephrol. 2010;21(6):966-73.
Chen X, Wan Z, Geng T, et al. Vitamin D status, vitamin D receptor polymorphisms, and risk of microvascular complications among individuals with type 2 diabetes: a prospective study. Diabetes Care. 2023;46(2):270-7.
Zhong P, Zhu Z, Wang Y, Huang W, He M, Wang W. Cardiovascular and microvascular outcomes according to vitamin D level and genetic variants among individuals with prediabetes: a prospective study. J Transl Med. 2023;21(1):724.
Deb DK, Sun T, Wong KE, et al. Combined vitamin D analog and AT1 receptor antagonists synergistically block the development of kidney disease in a model of type 2 diabetes. Kidney International. 2010;77(11):1000-9.
Qu Y, Wu Y, Jiang H. Research progress in the pharmacological actions of the multiple effects and selectivity of the vitamin D analog paricalcitol: a narrative review. Ann Palliat Med. 2021;10(10):11177-90.
Nakhoul N, Thawko T, Farber E, et al. The therapeutic effect of active vitamin d supplementation in preventing the progression of diabetic nephropathy in a diabetic mouse model. J Diabetes Res. 2020;2020:7907605.
Sözel H, Köksoy S, Ozdem S, Yılmaz F, Bora F, Ersoy FF. Lymphocyte and monocyte vitamin D receptor expression during paricalcitol or calcitriol treatments in patients with stage 5 chronic kidney disease. Int Urol Nephrol. 2020;52(8):1563-70.
Zeng JY, Wang Y, Hong FY, et al. Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of the VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy. Naunyn Schmiedebergs Arch Pharmacol. 2023.
Humalda JK, Goldsmith DJ, Thadhani R, de Borst MH. Vitamin D analogs to target residual proteinuria: potential impact on cardiorenal outcomes. Nephrol Dial Transplant. 2015;30(12):1988-94.
Freundlich M, Gamba G, Rodriguez-Iturbe B. Fibroblast growth factor 23-Klotho and hypertension: experimental and clinical mechanisms. Pediatr Nephrol. 2021;36(10):3007-22.
Jacobus CH, Holick MF, Shao Q, et al. Hypervitaminosis D is associated with drinking milk. N Engl J Med. 1992;326(18):1173-7.
Heaney RP. Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008;3(5):1535-41.
Akcay A, Ozdemir FN, Sezer S, et al. Association of vitamin D receptor gene polymorphisms with hypercalcemia in peritoneal dialysis patients. Perit Dial Int. 2005;25 Suppl 3:S52-5.
Wu CC, Liao MT, Hsiao PJ, et al. Antiproteinuria effect of calcitriol in patients with chronic kidney disease and vitamin d deficiency: A randomized controlled study. J Ren Nutr. 2020;30(3):200-7.
Bilezikian JP, Formenti AM, Adler RA, et al. Vitamin D: Dosing, levels, form, and route of administration. Does one approach fit all? Rev Endocr Metab Disord. 2021;22(4):1201-18.
Thadhani R, Appelbaum E, Pritchett Y, et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. Jama. 2012;307(7):674-84.
de Zeeuw D, Agarwal R, Amdahl M, et al. Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomized controlled trial. Lancet. 2010;376(9752):1543-51.
Li C, Ojeda-Thies C, Renz N, Margaryan D, Perka C, Trampuz A. The global state of clinical research and trends in periprosthetic joint infection: a bibliometric analysis. Int J Infect Dis. 2020;96:696-709.
Ke L, Lu C, Shen R, Lu T, Ma B, Hua Y. Knowledge mapping of drug-induced liver injury: a scientometric investigation (2010-2019). Front Pharmacol. 2020;11:842.
van Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics. 2010;84(2):523-38.
Yeung AWK, Mozos I. The innovative and sustainable use of dental panoramic radiographs for the detection of osteoporosis. Int J Environ Res Public Health. 2020;17(7).
Zhang XL, Zheng Y, Xia ML, et al. Knowledge domain and emerging trends in vinegar research: a bibliometric review of the literature from WoSCC. Foods. 2020;9(2).
Synnestvedt MB, Chen C, Holmes JH. CiteSpace II: visualization and knowledge discovery in bibliographic databases. AMIA Annu Symp Proc. 2005;2005:724-8.
Huang X, Fan X, Ying J, Chen S. Emerging trends and research foci in the gastrointestinal microbiome. J Transl Med. 2019;17(1):67.
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