Vitamin D receptor attenuates renal fibrosis by suppressing the renin-angiotensin system

Area of Science:

• Nephrology
• Endocrinology
• Molecular Biology

Background:

• Vitamin D analogs show renoprotective effects in kidney disease models.
• The specific mechanism of vitamin D's protective role in kidney fibrosis remains unclear.

Purpose of the Study:

• To investigate the role of the vitamin D receptor (VDR) in regulating renal fibrogenesis.
• To elucidate the VDR's influence on the renin-angiotensin system in kidney injury.

Main Methods:

• Utilized VDR-null and wild-type mice subjected to unilateral ureteral obstruction.
• Assessed renal damage, interstitial fibrosis, and expression of fibrotic/inflammatory markers.
• Evaluated the impact of angiotensin II (AngII) and losartan treatment on renal injury.

Main Results:

• VDR-null mice exhibited exacerbated renal damage, tubular atrophy, and interstitial fibrosis post-obstruction compared to wild-type.
• Significant upregulation of extracellular matrix proteins, profibrotic factors, and epithelial-to-mesenchymal transition was observed in VDR-null kidneys.
• Losartan treatment attenuated the enhanced interstitial fibrosis in VDR-null mice, implicating AngII.

Conclusions:

• The VDR plays a critical role in attenuating obstructive renal injury.
• VDR deficiency exacerbates renal fibrosis, partly through activation of the renin-angiotensin system.
• Targeting the VDR or renin-angiotensin system may offer therapeutic strategies for kidney fibrosis.