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Ischemia/reperfusion-induced Kidney Injury in Heterozygous PACAP-deficient Mice
E Laszlo1, A Varga2, K Kovacs3
1Department of Anatomy, MTA-PTE PACAP "Lendulet" Research Team, University of Pecs, Pecs, Hungary.
Transplantation Proceedings
|September 13, 2015
Summary
Partial deficiency of pituitary adenylate cyclase activating polypeptide (PACAP) exacerbates kidney injury. Heterozygous PACAP-deficient mice show worse outcomes after renal ischemia/reperfusion, highlighting PACAP's protective role.
Area of Science:
- Neuropeptide signaling
- Renal pathophysiology
- Molecular mechanisms of injury
Background:
- Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with known cytoprotective functions, including antiapoptotic, anti-inflammatory, and antioxidant actions.
- PACAP has demonstrated protective effects in kidney pathologies, such as ischemia/reperfusion (I/R)-induced kidney injury.
- PACAP-deficient mice exhibit increased vulnerability to harmful stimuli, with homozygous deficiency leading to more severe renal I/R damage.
Purpose of the Study:
- To investigate whether partial deficiency of the PACAP gene (in heterozygous mice) also leads to more severe damage following renal ischemia/reperfusion.
- To assess the impact of heterozygous PACAP deficiency on histological alterations, apoptotic markers, cytokine expression, and antioxidant enzyme activity post-renal I/R.
Main Methods:
- Renal ischemia/reperfusion was induced in wild-type and heterozygous PACAP-deficient mice for 45 or 60 minutes, followed by 2 weeks of reperfusion.
- Kidney tissues were evaluated histopathologically, and apoptotic markers, cytokine expression, and superoxide dismutase (SOD) activity were assessed 24 hours after 60 minutes of ischemia/reperfusion.
Main Results:
- Heterozygous PACAP-deficient mice exhibited significantly more severe histological alterations and higher histopathological scores compared to wild-type mice after renal I/R.
- Elevated levels of the proapoptotic marker pp38 MAPK and pro-inflammatory cytokines were observed in heterozygous mice post-I/R.
- Reduced activity of the antioxidant enzyme superoxide dismutase (SOD) was found in heterozygous PACAP-deficient mice following renal I/R.
Conclusions:
- Partial lack of PACAP gene function in heterozygous mice results in exacerbated kidney damage after renal ischemia/reperfusion.
- These findings confirm the role of PACAP as an endogenous protective factor in the kidney, crucial for mitigating I/R injury.
