Molecular mechanisms underlying the nephroprotective effects of PACAP in diabetes

Bánki, Eszter and Kovács, Krisztina and Nagy, Dániel and Juhász, Tamás and Degrell, Péter and Csanaky, Katalin and Kiss, Péter and Jancsó, Gábor and Tóth, Gábor and Tamás, Andrea and Reglődi, Dóra (2014) Molecular mechanisms underlying the nephroprotective effects of PACAP in diabetes. Journal of Molecular Neuroscience, 54 (3). pp. 300-309. ISSN 0895-8696, ESSN: 1559-1166

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Abstract

Diabetic nephropathy is the leading cause of end-stage renal failure and accounts for 30-40% of patients entering renal transplant programmes. Nephroprotective effects of the neuropeptide PACAP38 against diabetes has been shown previously, but the molecular mechanisms responsible for this effect remain unknown. In the present study, we showed that PACAP treatment counteracted the diabetes-induced increase in the level of the proapoptotic pp38MAPK and cleaved caspase-3 and also decreased the p60 subunit of NFκB. The examined antiapoptotic factors, including pAkt and pERK1/2 showed a slight increase in the diabetic kidneys, while PACAP treatment resulted in a notable elevation of these proteins. PCR and Western blot revealed the downregulation of fibrotic markers, like collagen IV and TGF-β1 in the kidney. PACAP treatment resulted in increased expression of the antioxidant glutathione. We conclude, that the nephroprotective effect of PACAP in diabetes is, at least partly, due to its antiapoptotic, antifibrotic and antioxidative effect in addition to the previously described antiinflammatory effect.

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