TRPC3 Is Downregulated in Primary Hyperparathyroidism

Int J Mol Sci. 2024 Apr 16;25(8):4392. doi: 10.3390/ijms25084392.

Abstract

Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.

Keywords: CaSR; TRPC3; TRPC6; human; immunohistochemistry; parathyroid gland; primary hyperparathyroidism.

MeSH terms

  • Adult
  • Aged
  • Down-Regulation*
  • Female
  • Humans
  • Hyperparathyroidism, Primary* / genetics
  • Hyperparathyroidism, Primary* / metabolism
  • Hyperparathyroidism, Primary* / pathology
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Parathyroid Glands* / metabolism
  • Parathyroid Glands* / pathology
  • Parathyroid Hormone / metabolism
  • TRPC Cation Channels* / genetics
  • TRPC Cation Channels* / metabolism
  • TRPC6 Cation Channel* / genetics
  • TRPC6 Cation Channel* / metabolism

Substances

  • TRPC Cation Channels
  • TRPC3 cation channel
  • TRPC6 Cation Channel
  • TRPC6 protein, human
  • Parathyroid Hormone

Grants and funding

This research received no external funding.