1. Academic Validation
  2. High sodium promotes the secretion and synthesis of PTH through PiT-1-IKKβ pathway in parathyroid gland in vitro

High sodium promotes the secretion and synthesis of PTH through PiT-1-IKKβ pathway in parathyroid gland in vitro

  • Clin Sci (Lond). 2023 Jun 28;137(12):947-962. doi: 10.1042/CS20220754.
Aiwen Shen 1 2 Yu Wang 1 2 Guoxin Ye 1 2 Jianping Mao 1 2 Qian Zhang 1 2 Jing Chen 1 2
Affiliations

Affiliations

  • 1 Department of Nephrology, Huashan Hospital, Fudan University, Shanghai, China.
  • 2 National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Abstract

Parathyroid hormone (PTH) is secreted by the parathyroid glands (PTGs) and is an important hormone regulating mineral metabolism. Previous studies reported that high sodium diet will cause the increase in serum PTH, but the specific mechanism is unknown. Consequently, the present study aims to investigate the effects and mechanisms of high sodium on PTH synthesis and secretion from PTGs. We developed a tissue culture model using normal rat PTGs, discovered that sodium elicited and promoted concentration-dependent and time-dependent PTH secretion. Changes in sodium-associated transporters from PTGs incubated with high sodium were thoroughly examined. Increased expression of sodium-phosphate cotransporter Slc20a1 (also known as PiT-1) was observed. Further tests revealed that PiT-1 activated the NF-κB signaling pathway, resulting in increased IKKβ phosphorylation, IKBα degradation, and increased p65 phosphorylation followed by nuclear entry, which led to increased PTH transcription. Meanwhile, IKKβ phosphorylated SNAP23, promoting exocytosis and eventually led to increased PTH secretion. In conclusion, our findings indicate that PiT-1 plays an important role in the increased secretion and synthesis of PTH directly induced by high sodium under physiological conditions, and may provide a potential therapeutic target for secondary hyperparathyroidism (SHPT).

Keywords

Nuclear factor-κB; Parathyroid hormone; PiT-1; Secondary hyperparathyroidism; Sodium.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10172
    99.51%, IKKβ 抑制剂
    IKK