Role of Nampt overexpression in a rat model of Hashimoto's thyroiditis and its mechanism of action

Exp Ther Med. 2020 Apr;19(4):2895-2900. doi: 10.3892/etm.2020.8539. Epub 2020 Feb 21.

Abstract

The present study was designed to investigate the role of nicotinamide phosphoribosyltransferase (Nampt) overexpression in a rat model of Hashimoto's thyroiditis (HT) and its mechanism of action. A rat model of HT was constructed, and the HT rats were injected with an adenoviral expression vector carrying the Nampt gene. The expression of Nampt and Toll-like receptor 4 (TLR4) in thyroid tissues was examined using immunohistochemistry (IHC), RT-qPCR and western blot analyses. Serum anti-thyroglobulin antibodies (TGAb) and anti-thyroid peroxidase antibodies (TPOAb) were measured using chemiluminescence method. Hematoxylin and eosin (H&E) and IHC staining of the rat thyroid tissues showed destroyed thyroid follicles and monocyte infiltration, as well as increased Nampt expression in the thyroid tissues of rats with HT. Furthermore, it was found that Nampt overexpression led to increased severity of inflammatory infiltration in thyroid tissues and increased levels of TPOAb in the serum of HT rats; however, the serum TGAb level was not affected by Nampt overexpression. In addition, Nampt overexpression promoted TLR4 expression in HT rats. In conclusion, it was demonstrated that Nampt was strongly expressed in the capillary region of HT rats thyroid tissues. The Nampt mRNA level was increased but the Nampt protein level was decreased in the thyroid tissues of rats with HT. Nampt overexpression has a promotive effect on HT progression, and this effect was related to TLR4. This study suggests that inhibition of Nampt activity may be valuable in the treatment of HT.

Keywords: Hashimoto's thyroiditis; Nampt; Toll-like receptor 4; anti-thyroglobulin antibodies; anti-thyroid peroxidase antibodies; nicotinamide phosphoribosyltransferase.