Connexin Expression in Human Minor Salivary Glands: An Immunohistochemical Microscopy Study

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2022 Sep 23

PMID 36144660

Authors

Alessandra Falleni

Stefania Moscato

Giovanni Fulvio

Enza Polizzi

Margherita Bernardeschi

Francesco Bianchi

Valentina Donati

Manuela Cabiati

Chiara Ippolito

Silvia Del Ry

Chiara Baldini

Letizia Mattii

Affiliations

Soon will be listed here.

Abstract

Connexins (Cxs) are transmembrane proteins involved in the formation of hemichannels and gap junctions (GJs). GJs are involved in various physiological functions, including secretion in glandular tissue. It has been demonstrated that Cx26, Cx32, and Cx43 are mainly expressed in glands, but no data are available in human salivary glands to date. The aim of our study was to investigate the presence and the localization of Cxs in human minor labial salivary glands. Immunofluorescence and immunoelectron microscopy were employed to evaluate the Cx26, Cx32, and Cx43 protein in human labial salivary gland biopsies (hLSGBs). RT-PCR was also used to detect their mRNA expression. Cx expression was found at both the mRNA and protein levels in all hLSGBs analysed. Cxs were observed at the level of the duct and acinar cells, as well as in myoepithelial cells. The localization of the three Cx types was very similar, suggesting colocalization of these Cxs in the same connexons. These results demonstrated the presence of Cxs in human salivary glands for the first time. Moreover, the few samples with primary Sjögren's Syndrome analysed only by immunofluorescence showed an alteration of the Cx expression, indicating that these proteins could be involved in salivary gland dysfunctions.

Citing Articles

The role and mechanism of heme oxygenase-1 in arrhythmias.

Liu H, Zhang L, Yang F, Qian L, Wang R J Mol Med (Berl). 2024; 102(8):1001-1007.

PMID: 38937302 DOI: 10.1007/s00109-024-02462-4.

References

Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A . Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol. 2002; 3(7):RESEARCH0034. PMC: 126239. DOI: 10.1186/gb-2002-3-7-research0034. View

Smyth J, Shaw R . Autoregulation of connexin43 gap junction formation by internally translated isoforms. Cell Rep. 2013; 5(3):611-8. PMC: 3898934. DOI: 10.1016/j.celrep.2013.10.009. View

Qin H, Shao Q, Thomas T, Kalra J, Alaoui-Jamali M, Laird D . Connexin26 regulates the expression of angiogenesis-related genes in human breast tumor cells by both GJIC-dependent and -independent mechanisms. Cell Commun Adhes. 2003; 10(4-6):387-93. DOI: 10.1080/cac.10.4-6.387.393. View

Shah A, Mulla A, Mayank M . Pathophysiology of myoepithelial cells in salivary glands. J Oral Maxillofac Pathol. 2016; 20(3):480-490. PMC: 5051298. DOI: 10.4103/0973-029X.190952. View

Lenzi P, Ferese R, Biagioni F, Fulceri F, Busceti C, Falleni A . Rapamycin Ameliorates Defects in Mitochondrial Fission and Mitophagy in Glioblastoma Cells. Int J Mol Sci. 2021; 22(10). PMC: 8161366. DOI: 10.3390/ijms22105379. View

Laird D . Life cycle of connexins in health and disease. Biochem J. 2006; 394(Pt 3):527-43. PMC: 1383703. DOI: 10.1042/BJ20051922. View

Sosinsky G, Nicholson B . Structural organization of gap junction channels. Biochim Biophys Acta. 2005; 1711(2):99-125. DOI: 10.1016/j.bbamem.2005.04.001. View

Shen D, Ono K, Do Q, Ohyama H, Nakamura K, Obata K . Clinical anatomy of the inferior labial gland: a narrative review. Gland Surg. 2021; 10(7):2284-2292. PMC: 8340335. DOI: 10.21037/gs-21-143. View

Martin P, Evans W . Incorporation of connexins into plasma membranes and gap junctions. Cardiovasc Res. 2004; 62(2):378-87. DOI: 10.1016/j.cardiores.2004.01.016. View

10.

Mroue R, Inman J, Mott J, Budunova I, Bissell M . Asymmetric expression of connexins between luminal epithelial- and myoepithelial- cells is essential for contractile function of the mammary gland. Dev Biol. 2014; 399(1):15-26. PMC: 4996272. DOI: 10.1016/j.ydbio.2014.11.026. View

11.

Meda P, Pepper M, Traub O, Willecke K, Gros D, Beyer E . Differential expression of gap junction connexins in endocrine and exocrine glands. Endocrinology. 1993; 133(5):2371-8. DOI: 10.1210/endo.133.5.8404689. View

12.

Ko Y, Yeh H, Rothery S, Dupont E, Coppen S, Severs N . Connexin make-up of endothelial gap junctions in the rat pulmonary artery as revealed by immunoconfocal microscopy and triple-label immunogold electron microscopy. J Histochem Cytochem. 1999; 47(5):683-92. DOI: 10.1177/002215549904700510. View

13.

Zhu Y . Gap Junction-Dependent and -Independent Functions of Connexin43 in Biology. Biology (Basel). 2022; 11(2). PMC: 8869330. DOI: 10.3390/biology11020283. View

14.

Cabiati M, Sapio A, Salvadori C, Burchielli S, Carlucci L, Mattii L . Evaluation of transcriptional levels of the natriuretic peptides, endothelin-1, adrenomedullin, their receptors and long non-coding RNAs in rat cardiac tissue as cardiovascular biomarkers of aging. Peptides. 2019; 123:170173. DOI: 10.1016/j.peptides.2019.170173. View

15.

Shimono M, Lee C, Matsuzaki H, Ishikawa H, Inoue T, Hashimoto S . Connexins in salivary glands. Eur J Morphol. 2000; 38(4):257-61. DOI: 10.1076/0924-3860(200010)38:4;1-o;ft257. View

16.

Falleni A, Moscato S, Sabbatini A, Bernardeschi M, Bianchi F, Cecchettini A . Subcellular Localization of Connexin 26 in Cardiomyocytes and in Cardiomyocyte-Derived Extracellular Vesicles. Molecules. 2021; 26(21). PMC: 8587102. DOI: 10.3390/molecules26216726. View

17.

Walcott B, Moore L, Birzgalis A, Claros N, Valiunas V, Ott T . Role of gap junctions in fluid secretion of lacrimal glands. Am J Physiol Cell Physiol. 2002; 282(3):C501-7. DOI: 10.1152/ajpcell.00004.2001. View

18.

Kidder G, Winterhager E . Physiological roles of connexins in labour and lactation. Reproduction. 2015; 150(4):R129-36. DOI: 10.1530/REP-15-0134. View

19.

Cabiati M, Salvadori C, Sapio A, Burchielli S, Carlucci L, Moscato S . Aging and biomarkers: Transcriptional levels evaluation of Osteopontin/miRNA-181a axis in hepatic tissue of rats in different age ranges. Exp Gerontol. 2020; 133:110879. DOI: 10.1016/j.exger.2020.110879. View

20.

Actis A, Lampe P, Eynard A . Cellular basis and clinical implications of biological markers in salivary tissues: their topological distribution in murine submandibular gland. Oral Oncol. 2002; 38(5):441-9. DOI: 10.1016/s1368-8375(01)00091-4. View