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

Aiyuan  Cai; Qingpeng  Hu; Haixia  Wu; Zilong  Li; Yuanhong  Lin; Jiaohua  Yu; Hailong  Huang; Ruizhong  Zhang; Jing  Xiao; Ping  Liu

doi:10.54817/IC.v66n3a06

Aiyuan Cai Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, Ch https://orcid.org/0000-0002-2978-5476
Qingpeng Hu Department of Pediatrics, the Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan, C https://orcid.org/0009-0002-0586-5364
Haixia Wu Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, China https://orcid.org/0009-0009-1503-8187
Zilong Li Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, China https://orcid.org/0009-0002-9174-9246
Yuanhong Lin Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China. https://orcid.org/0009-0009-5397-2587
Jiaohua Yu Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, China https://orcid.org/0009-0002-1098-7913
Hailong Huang Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, China https://orcid.org/0009-0001-7321-5710
Ruizhong Zhang Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, Ch https://orcid.org/0009-0005-9678-3226
Jing Xiao Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, China https://orcid.org/0009-0001-4989-3909
Ping Liu Department of Pediatrics, Longhua District People’s Hospital, Shenzhen, Guangdong, Chi https://orcid.org/0009-0007-9178-5278

DOI: https://doi.org/10.54817/IC.v66n3a06

Keywords: vitamin D, hypothyroidism, kidney injuries, epithelial-mesenchymal transition, TRAF6 protein, MAP3K7 protein (TAK1), signal transduction

Abstract

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-β activated 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.

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

Vitamina D atenúa la transformación mesenquímica-epitelial de células epiteliales tubulares renales a través de la vía de señalización Traf6/TAK1 en ratas bebé con hipotiroidismo.

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