{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T21:54:32Z","timestamp":1778968472150,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T00:00:00Z","timestamp":1713225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014especially TRPC3 and TRPC6\u2014in 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.<\/jats:p>","DOI":"10.3390\/ijms25084392","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T08:22:44Z","timestamp":1713342164000},"page":"4392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["TRPC3 Is Downregulated in Primary Hyperparathyroidism"],"prefix":"10.3390","volume":"25","author":[{"given":"Emilie","family":"Kirstein","sequence":"first","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Schaudien","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hanover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathias","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Pathology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coline M.","family":"Diebolt","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9648-8834","authenticated-orcid":false,"given":"Alessandro","family":"Bozzato","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology, Head and Neck Surgery, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7788-1796","authenticated-orcid":false,"given":"Thomas","family":"Tschernig","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6746-3681","authenticated-orcid":false,"given":"Colya N.","family":"Englisch","sequence":"additional","affiliation":[{"name":"Institute for Anatomy and Cell Biology, Saarland University, 66421 Homburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","unstructured":"Brown, M.B., and Limaiem, F. (2023). StatPearls, StatPearls."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e132496","DOI":"10.1172\/jci.insight.132496","article-title":"Control of PTH secretion by the TRPC1 ion channel","volume":"5","author":"Onopiuk","year":"2020","journal-title":"JCI Insight"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.beem.2013.02.006","article-title":"Role of the calcium-sensing receptor in extracellular calcium homeostasis","volume":"27","author":"Brown","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1002\/jbmr.4665","article-title":"Epidemiology, Pathophysiology, and Genetics of Primary Hyperparathyroidism","volume":"37","author":"Minisola","year":"2022","journal-title":"J. Bone Miner. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1677\/JME-09-0138","article-title":"Expression and association of TRPC subtypes with Orai1 and STIM1 in human parathyroid","volume":"44","author":"Lu","year":"2010","journal-title":"J. Mol. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ceca.2005.06.012","article-title":"Calcium-dependent regulation of exocytosis","volume":"38","author":"Barclay","year":"2005","journal-title":"Cell Calcium"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1159\/000189144","article-title":"Oxyphil cell function in secondary parathyroid hyperplasia","volume":"73","author":"Tanaka","year":"1996","journal-title":"Nephron"},{"key":"ref_8","first-page":"N68","article-title":"Clinical presentation of primary hyperparathyroidism in Europe--nationwide cohort analysis on mortality from nonmalignant causes","volume":"17","author":"Nilsson","year":"2002","journal-title":"J. Bone Miner. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nrendo.2017.104","article-title":"Primary hyperparathyroidism","volume":"14","author":"Walker","year":"2018","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1210\/endrev\/bnad009","article-title":"Molecular and Clinical Spectrum of Primary Hyperparathyroidism","volume":"44","author":"Jha","year":"2023","journal-title":"Endocr. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.1111\/bph.12414","article-title":"Transient receptor potential (TRP) channels: A clinical perspective","volume":"171","author":"Kaneko","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1096\/fj.08-119495","article-title":"Physiology and pathophysiology of canonical transient receptor potential channels","volume":"23","author":"Abramowitz","year":"2009","journal-title":"FASEB J."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Englisch, C.N., Paulsen, F., and Tschernig, T. (2022). TRPC Channels in the Physiology and Pathophysiology of the Renal Tubular System: What Do We Know?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010181"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"152192","DOI":"10.1016\/j.aanat.2023.152192","article-title":"New insights in the renal distribution profile of TRPC3\u2014Of mice and men","volume":"252","author":"Diebolt","year":"2023","journal-title":"Ann. Anat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/cphy.c150052","article-title":"Calcium Homeostasis in Health and in Kidney Disease","volume":"6","author":"Moe","year":"2016","journal-title":"Compr. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"45","DOI":"10.2741\/3230","article-title":"The integrative function of TRPC channels","volume":"14","author":"Kiselyov","year":"2009","journal-title":"Front. Biosci. (Landmark Ed.)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"107497","DOI":"10.1016\/j.pharmthera.2020.107497","article-title":"TRPC channels: Structure, function, regulation and recent advances in small molecular probes","volume":"209","author":"Wang","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4161\/chan.2.2.6015","article-title":"TRPC3\/6\/7: Topical aspects of biophysics and pathophysiology","volume":"2","author":"Eder","year":"2008","journal-title":"Channels"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1038\/s41422-018-0038-2","article-title":"Structure of the receptor-activated human TRPC6 and TRPC3 ion channels","volume":"28","author":"Tang","year":"2018","journal-title":"Cell Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.beem.2013.02.009","article-title":"The CASR gene: Alternative splicing and transcriptional control, and calcium-sensing receptor (CaSR) protein: Structure and ligand binding sites","volume":"27","author":"Hendy","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e18629","DOI":"10.1016\/j.heliyon.2023.e18629","article-title":"A high-salt diet promotes hypertrophic scarring through TRPC3-mediated mitochondrial Ca(2+) homeostasis dysfunction","volume":"9","author":"Xia","year":"2023","journal-title":"Heliyon"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"11011","DOI":"10.1073\/pnas.1309531110","article-title":"Canonical transient receptor potential 3 channels regulate mitochondrial calcium uptake","volume":"110","author":"Feng","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"ra50","DOI":"10.1126\/scisignal.2003701","article-title":"Transient receptor potential channels function as a coincidence signal detector mediating phosphatidylserine exposure","volume":"6","author":"Harper","year":"2013","journal-title":"Sci. Signal"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"36598","DOI":"10.1074\/jbc.M113.488122","article-title":"Transient receptor potential channel 6 (TRPC6) protects podocytes during complement-mediated glomerular disease","volume":"288","author":"Kistler","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"G144","DOI":"10.1152\/ajpgi.00021.2019","article-title":"Calcium-sensing receptor deletion in the mouse esophagus alters barrier function","volume":"318","author":"Nakhoul","year":"2020","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ram, S., Vizcarra, P., Whalen, P., Deng, S., Painter, C.L., Jackson-Fisher, A., Pirie-Shepherd, S., Xia, X., and Powell, E.L. (2021). Pixelwise H-score: A novel digital image analysis-based metric to quantify membrane biomarker expression from immunohistochemistry images. PLoS ONE, 16.","DOI":"10.1101\/2021.01.06.425539"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/978-1-4939-8935-5_25","article-title":"An Introduction to the Performance of Immunohistochemistry","volume":"1897","author":"Magaki","year":"2019","journal-title":"Methods Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Pillai-Kastoori, L., Schutz-Geschwender, A.R., and Harford, J.A. (2020). A systematic approach to quantitative Western blot analysis. Anal. Biochem., 593.","DOI":"10.1016\/j.ab.2020.113608"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Taylor, S.C., and Posch, A. (2014). The design of a quantitative western blot experiment. Biomed. Res. Int., 2014.","DOI":"10.1155\/2014\/361590"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1159\/000503724","article-title":"The Effect and Mechanism of TRPC1, 3, and 6 on the Proliferation, Migration, and Lumen Formation of Retinal Vascular Endothelial Cells Induced by High Glucose","volume":"63","author":"Lang","year":"2020","journal-title":"Ophthalmic Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.3892\/mmr.2017.6744","article-title":"Altered expression of PPAR-gamma and TRPC in neonatal rats with persistent pulmonary hypertension","volume":"16","author":"Du","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"Uhlen","year":"2015","journal-title":"Science"},{"key":"ref_33","unstructured":"(2024, March 01). Available online: https:\/\/www.proteinatlas.org\/ENSG00000138741-TRPC3\/tissue\/parathyroid+gland."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s40618-021-01646-w","article-title":"CaSR expression in normal parathyroid and PHPT: New insights into pathogenesis from an autopsy-based study","volume":"45","author":"Agarwal","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1007\/s12022-018-9524-9","article-title":"Clinical Impact of p27(Kip1) and CaSR Expression on Primary Hyperparathyroidism","volume":"29","author":"Aydogan","year":"2018","journal-title":"Endocr. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.jss.2023.09.001","article-title":"Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue","volume":"293","author":"Worth","year":"2024","journal-title":"J. Surg. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1530\/eje.1.02007","article-title":"Relationship between parathyroid calcium-sensing receptor expression and potency of the calcimimetic, cinacalcet, in suppressing parathyroid hormone secretion in an in vivo murine model of primary hyperparathyroidism","volume":"153","author":"Kawata","year":"2005","journal-title":"Eur. J. Endocrinol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:28:47Z","timestamp":1760106527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":37,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084392"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084392","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]}}}