Vitamin D attenuates epithelial-mesenchymal transition of renal tubular epithelial cells in infant rats with hypothyroidism via the Traf6/TAK1 signalling pathway.

In the hypothyroidism(HT) state, renal hemodynamics is disor-dered, oxidative stress is intensified, and inflammatory factors are activated. Vi-tamin D (VD) not only regulates calcium and phosphorus metabolism, but its active form (1,25-dihydroxyvitamin D) could also exert anti-inflammatory and an-ti-fibrotic effects by binding with the vitamin D receptor (VDR) widely distributed in the kidney. This study aimed to elucidate the impact of VD on the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells in HT-induced re-nal injury in young rats, as well as its regulatory mechanism involving the tumor necrosis factor receptor-associated factor 6 (Traf6)/transforming growth factor-βactivated kinase 1 (TAK1) pathway. An HT model in young rats was established via propylthiouracil (PTU) gavage, and a functional rescue experiment was con-ducted by overexpressing TAK1 (pcDNA3.1-TAK1). The animals were divided into five groups: normal, HT, low-dose VD (HT+VD-L), high-dose VD (HT+VD-H), and HT+VD-H+pcDNA3.1-TAK1 (HT+VD-H+pc). Each group consisted of 10 rats. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured using an automatic biochemical analyzer. Renal apoptosis (TUNEL), TGF-β1/α-SMA/E-cadherin (immunohistochemistry), and Bcl-2/Bax/Traf6/TAK1/p-TAK1 (Western blot) expressions were assessed in renal tissue. VD significantly reduced Scr and BUN levels in the serum of HT young rats, downregulated renal tissue apoptosis, decreased TGF-β1 and α-SMA expressions, and upregulated E-cadherin expression. Additionally, VD inhibited Traf6, p-TAK1, and Bax expressions while increasing Bcl-2 expression. All differences were statistically significant.