Ochratoxin A induces glomerular injury through activating the ERK/NF-κB signaling pathway

Area of Science:

• Toxicology
• Nephrology
• Molecular Biology

Background:

• Ochratoxin A (OTA) is a known nephrotoxin primarily affecting proximal tubules.
• The impact of OTA on glomerular structures and the underlying mechanisms remain underexplored.

Purpose of the Study:

• To investigate OTA-induced glomerular injury in vivo and in vitro.
• To elucidate the molecular mechanisms, particularly the role of signaling pathways, in OTA nephrotoxicity.

Main Methods:

• Mice were administered varying doses of OTA intraperitoneally for 3 weeks.
• Human mesangial cells (HMC) were exposed to OTA in vitro.
• Key molecular markers and signaling pathways (TNF-α, IL-6, COX-2, TGF-β, α-SMA, vimentin, ERK1/2, NF-κB) were analyzed.

Main Results:

• OTA exposure led to decreased weight gain, altered kidney index, and elevated serum creatinine and blood urea nitrogen in mice.
• Histopathological examination revealed glomerular fragmentation and atrophy.
• OTA upregulated pro-inflammatory and fibrotic markers (IL-6, TGF-β, α-SMA, vimentin) and activated the ERK/NF-κB pathway in both mice and HMC.

Conclusions:

• OTA induces glomerular injury through the activation of the ERK/NF-κB signaling pathway.
• This study provides novel insights into the mechanisms of OTA-induced nephrotoxicity, highlighting glomerular targets.
• Findings suggest potential therapeutic targets for mitigating OTA-related kidney damage.