Nicotinamide Phosphoribosyltransferase (NAMPT) Improves Kidney Injury and Promotes Kidney Regeneration of Adult Zebrafish

Background: NAMPT is a known adipokine which improves insulin resistance in obesity and have an anti-diabetic effect. However, its role remains uncertain in kidney injury and regeneration. In this study, we investigated the role of NAMPT on puromycin-induced kidney injury and regeneration of adult zebrafish model. Methods: We injected 100ug of puromycin or/and 500ng of NAMPT via intraperitoneal injection into adult wild zebrafish, which were sacrificed at 1, 3, 5, 7, and 14 dpi. To investigate the role of NAMPT in kidney regeneration, we generated NAMPT knock-out zebrafish, then observed nephron injury and regeneration. Results: Larva kidney showed only namptb gene expression and adult kidney presented both nampta and namptb gene expressions. Puromycin increased both nampta and namptb gene expressions. And puromycin also increased NAMPT protein expression of adult kidney. Compared to controls, puromycin-induced NAMPT protein synthesis was increased from 1 dpi until 7 dpi. NAMPT was not expressed on podocytes of glomeruli, but identified on interstitial and tubular cells of kidney in adult zebrafish. Especially, IF staining showed NAMPT expression on the apical area of tubular cells and intranuclear area of interstitial cells between 7 dpi and 14 dpi. NAMPT treatment recovered puromycin-induced nephron loss and tubular regeneration of adult zebrafish at 7 dpi and 14 dpi. This result also was identified by in situ hybridization of lhx1a as a regeneration marker. Finally, NAMPT knock-out zebrafish showed smaller number of nephrons in puromycin-induced kidney regeneration than that of puromycin-treated wild zebrafish. Conclusion: From these results, NAMPT improved puromycin-induced kidney injury and enhanced kidney regeneration in adult zebrafish. Moreover, NAMPT showed the key role in nephron regeneration. Funding: Government Support – Non-U.S.