Calcitriol regulates angiotensin-converting enzyme and angiotensin converting-enzyme 2 in diabetic kidney disease.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro bench study
PubMed 26968558 · doi:10.1007/s11033-016-3971-5
What was done
Streptozotocin (STZ)-induced diabetic rats were treated with calcitriol for 16 weeks to assess its effects on proteinuria, calcium-phosphorus metabolism, and renal ACE and ACE2 expression. In parallel, rat renal tubular epithelial cells (NRK-52E) exposed to high glucose were treated with calcitriol and specific MAPK pathway inhibitors (p38 MAPK inhibitor SB203580, ERK inhibitor FR180204, and JNK inhibitor SP600125) to evaluate signaling mechanisms regulating ACE and ACE2 expression.
What was found
In diabetic rats, both ACE and ACE2 levels increased compared to control rats, but a disproportionate increase in ACE raised the ACE/ACE2 ratio. Calcitriol treatment reduced proteinuria without affecting calcium-phosphorus metabolism, reduced ACE levels and the ACE/ACE2 ratio, and increased ACE2 levels. In cell culture, high glucose up-regulated ACE (prevented by the p38 inhibitor) and down-regulated ACE2 (prevented by the ERK inhibitor). Calcitriol inhibited p38 MAPK and ERK phosphorylation (without affecting JNK) and attenuated both ACE up-regulation and ACE2 down-regulation under high-glucose conditions. Specific numerical values and effect sizes were not reported in the abstract.
Why it matters
The findings suggest that calcitriol provides renoprotection in experimental diabetic kidney disease by restoring the balance of the renal ACE/ACE2 axis through modulation of p38 MAPK and ERK signaling pathways.
Limits
The study is restricted to a chemically induced rodent model and an in vitro rat cell line, meaning relevance to human diabetic nephropathy remains unestablished. The abstract does not report animal sample sizes, cell replicate numbers, or quantitative values with statistical variance.
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