期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 186, 期 4, 页码 794-804出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2015.11.015
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资金
- Dutch Diabetes Fund Ruby Diabetes Research grant [2009.80.118]
- Genzyme Renal Innovations Program grant
- Dutch Kidney Foundation Kolff Career Stimulation [KJPB 07.0001, 13OKS023]
- Dutch Kidney Foundation grant [C09.2331]
- Marie Curie grant [ITN287813]
- EuTRiPD
- Dutch Organization for Scientific Research grant [NWO-ALW 818.02.001]
- European Young Investigator award
- Netherlands Organisation for Scientific Research Vici grant [016.130.668]
Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D-3 deficiency as a result of reduced renal 1 alpha-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D Levels and proteinuria. Herein, we showed that 1,25-vitamin D-3-deficient 25-hydroxy-vitamin-D-3-1 alpha-hydroxylase knockout mice and 1,25-vitamin D-3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D-3-deficient animals. Supplementation with 1,25-vitamin D-3 or 1,25-vitamin D-2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D-3-deficient animal, thereby preserving and restoring renal function, respectively. The effect of 1,25-vitamin D-3 deficiency and 1,25-vitamin D-3 and 1,25-vitamin D-2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25-vitamin D-3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury.
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