Details

Autor(en) / Beteiligte

• YOULI WANG
• DEB, Dilip K
• ZHONGYI ZHANG
• TAO SUN
• WEICHENG LIU
• YOON, Dosuk
• JUANKONG
• YUNZI CHEN
• CHANG, Anthony
• YAN CHUN LI

Titel

Vitamin D Receptor Signaling in Podocytes Protects against Diabetic Nephropathy

Ist Teil von

• Journal of the American Society of Nephrology, 2012-12, Vol.23 (12), p.1977-1986

Ort / Verlag

Washington, DC: American Society of Nephrology

Erscheinungsjahr

2012

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Vitamin D and its analogs have antiproteinuric activity and podocytes express the vitamin D receptor, but whether vitamin D signaling in podocytes accounts for this renoprotection is unknown. To investigate this question, we used the 2.5 kb podocin promoter to target Flag-tagged human vitamin D receptor (hVDR) to podocytes in DBA/2J mice. After the induction of diabetes with streptozotocin, transgenic mice had less albuminuria than wild-type controls. In transgenic mice, a low dose of the vitamin D analog doxercalciferol prevented albuminuria, markedly attenuated podocyte loss and apoptosis, and reduced glomerular fibrosis, but it had little effect on the progression of diabetic nephropathy in wild-type mice. Moreover, reconstitution of VDR-null mice with the hVDR transgene in podocytes rescued VDR-null mice from severe diabetes-related renal damage. In culture, 1,25-dihydroxyvitamin D suppressed high-glucose-induced apoptosis of podocytes by blocking p38- and ERK-mediated proapoptotic pathways. Taken together, these data provide strong evidence that vitamin D/VDR signaling in podocytes plays a critical role in the protection of the kidney from diabetic injury.