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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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Paricalcitol prevents MAPK pathway activation and inflammation in adriamycin-induced kidney injury in rats

Amanda Lima Deluque1, Lucas Ferreira de Almeida2, Beatriz Magalhães Oliveira1

  • 1Laboratory of Renal Physiology, Department of Physiology, Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.

Journal of Pathology and Translational Medicine
|August 26, 2024
PubMed
Abstract

Insights

Paricalcitol, an activated vitamin D analog, reduces kidney inflammation and cell proliferation in Adriamycin-induced nephropathy. This highlights its potential renoprotective role in chronic kidney disease (CKD).

Area of Science:

  • Nephrology
  • Pharmacology
  • Cell Biology

Background:

  • Mitogen-activated protein kinase (MAPK) pathway activation drives uncontrolled cell proliferation during inflammation, mimicking chronic kidney disease (CKD) mechanisms.
  • Adriamycin (ADR)-induced nephropathy (ADRN) in rats activates MAPK and pro-inflammatory cytokines, similar to CKD.
  • Vitamin D receptor (VDR) activation suppresses renal inflammatory markers and may reduce cellular proliferation.

Purpose of the Study:

  • To evaluate the renoprotective effects of paricalcitol, a VDR activator, on renal inflammation and cell proliferation in a rat model of ADRN.

Main Methods:

  • Male Sprague-Dawley rats received paricalcitol or vehicle via osmotic minipump.
  • ADR or vehicle was injected 2 days post-implantation.
  • Experimental groups included control, paricalcitol, ADR, and ADR + paricalcitol.

Main Results:

  • Paricalcitol activated VDR, evidenced by increased CYP24A1 expression.
  • It prevented macrophage infiltration, pro-inflammatory cytokine secretion (TNF-α, IL-1β), and modulated arginase expression.
  • Paricalcitol attenuated MAPK pathways, increased zonula occludens-1, reduced cell proliferation (PCNA), and inhibited the SDF-1α/CXCR4/β-catenin pathway.

Conclusions:

  • Paricalcitol demonstrates a renoprotective effect by modulating renal inflammation and cell proliferation in ADRN.
  • These findings suggest VDR activation as a potential therapeutic strategy for treating CKD.
Keywords:
Cellular proliferationInflammationMacrophagesRenal insufficiencyVitamin D

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