Molecular mechanisms of endoplasmic reticulum stress-mediated acute kidney injury in juvenile rats and the protective role of mesencephalic astrocyte-derived neurotrophic factor.

This article investigates the role of endoplasmic reticulum (ER) stress in pediatric acute kidney injury (AKI) and evaluates the therapeutic effects of mesencephalic astrocyte-derived neurotrophic factor (MANF) using a juvenile rat model and HK-2 cell line. The study demonstrates that ischemia-reperfusion injury (IRI)-induced AKI leads to increased ER stress, oxidative stress, apoptosis, and inflammation, which are mitigated by MANF treatment. MANF administration improved renal function and morphology by reducing biomarkers of kidney injury, inflammatory cytokines, ER stress markers (IRE1, PERK, ATF6, CHOP), and autophagy-related proteins, while inhibiting the JNK/TLR4/NF-κB signaling pathway. These findings suggest that MANF has potential as a novel therapeutic agent for pediatric AKI by alleviating ER stress-mediated cellular damage and inflammatory responses.