Chronic hypoxia promoted pulmonary arterial smooth muscle cells proliferation through upregulated calcium-sensing receptorcanonical transient receptor potential 1/6 pathway.
calcium-sensing receptor
canonical transient receptor potential proteins
pulmonary arterial hypertension
pulmonary arterial smooth muscle cells
pulmonary vascular remodeling
Journal
Microcirculation (New York, N.Y. : 1994)
ISSN: 1549-8719
Titre abrégé: Microcirculation
Pays: United States
ID NLM: 9434935
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
28
04
2021
received:
28
06
2020
accepted:
11
05
2021
pubmed:
20
5
2021
medline:
8
2
2022
entrez:
19
5
2021
Statut:
ppublish
Résumé
Although both calcium-sensing receptor (CaSR) and canonical transient receptor potential (TRPC) proteins contribute to chronic hypoxia (CH)-induced pulmonary arterial smooth muscle cells (PASMCs) proliferation, the relationship between CaSR and TRPC in hypoxic PASMCs proliferation remains poorly understood. The goal of this study was to identify that CH promotes PASMCs proliferation through CaSR-TRPC pathway. Rat PASMCs were isolated and treated with CH. Cell proliferation was assessed by cell counting, CCK-8 assay, and EdU incorporation. CaSR and TRPC expressions were determined by qPCR and Western blotting. Store-operated Ca In PASMCs, CH enhanced the cell number, cell viability and DNA synthesis, which is accompanied by upregulated expression of CaSR, TRPC1 and TRPC6. Negative CaSR modulators (NPS2143, NPS2390) inhibited, whereas positive modulators (spermine, R568) enhanced, the CH-induced increases in cell number, cell viability and DNA synthesis in PASMCs. Knockdown of CaSR by siRNA inhibited the CH-induced upregulation of TRPC1 and TRPC6 and enhancement of SOCE and attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. However, neither siTRPC1 nor siTRPC6 had an effect on the CH-induced CaSR upregulation, although both significantly attenuated the CH-induced enhancements of cell number, cell viability and DNA synthesis in PASMCs. These results demonstrate that upregulated CaSR-TRPC1/6 pathway mediating PASMCs proliferation is an important pathogenic mechanism under hypoxic conditions.
Substances chimiques
TRPC Cation Channels
0
TRPC6 Cation Channel
0
transient receptor potential cation channel, subfamily C, member 1
0
DNA
9007-49-2
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12715Informations de copyright
© 2021 John Wiley & Sons Ltd.
Références
Zhang L, Ma C, Gu R, et al. Paeonol regulates hypoxia-induced proliferation of pulmonary artery smooth muscle cells via ekr 1/2 signalling. Eur J Pharmacol. 2018;834:257-265.
Cai P, Kovacs L, Dong S, Wu G, Su Y. Bmp4 inhibits pdgf-induced proliferation and collagen synthesis via pka-mediated inhibition of calpain-2 in pulmonary artery smooth muscle cells. Am J Physiol Lung Cell Mol Physiol. 2017;312:L638-L648.
Chen J, Guo J, Cui X, et al. The long noncoding rna lnrpt is regulated by pdgf-bb and modulates the proliferation of pulmonary artery smooth muscle cells. Am J Respir Cell Mol Biol. 2018;58:181-193.
Ikeda K, Nakajima T, Yamamoto Y, et al. Roles of transient receptor potential canonical (trpc) channels and reverse-mode Na+/Ca2+ exchanger on cell proliferation in human cardiac fibroblasts: effects of transforming growth factor beta1. Cell Calcium. 2013;54:213-225.
Li MQ, Chen CH, Zhou Z, Xu SC, Yu ZP. A trpc1-mediated increase in store-operated Ca2+ entry is required for the proliferation of adult hippocampal neural progenitor cells. Cell Calcium. 2012;51:486-496.
El Boustany C, Bidaux G, Enfissi A, Delcourt P, Prevarskaya N, Capiod T. Capacitative calcium entry and transient receptor potential canonical 6 expression control human hepatoma cell proliferation. Hepatology. 2008;47:2068-2077.
Jiang YL, Zhou YM, Peng GY, et al. Trpc channels mediated calcium entry is required for proliferation of human airway smooth muscle cells induced by nicotine-nachr. Biochimie. 2019;158:139-148.
Yu Y, Fantozzi I, Remillard CV, et al. Enhanced expression of transient receptor potential channels in idiopathic pulmonary arterial hypertension. Proc Natl Acad Sci USA. 2004;101:13861-13866.
Wang J, Weigand L, Lu WJ, Sylvester JT, Semenza GL, Shimoda LA. Hypoxia inducible factor 1 mediates hypoxia-induced trpc expression and elevated intracellular Ca2+ in pulmonary arterial smooth muscle cells. Circ Res. 2006;98:1528-1537.
Lu WJ, Wang J, Shimoda LA, Sylvester JT. Differences in stim1 and trpc expression in proximal and distal pulmonary arterial smooth muscle are associated with differences in Ca2+ responses to hypoxia. Am J Physiol-Lung C. 2008;295:L104-L113.
Zhang Y, Lu WJ, Yang K, et al. Bone morphogenetic protein 2 decreases trpc expression, store-operated Ca2+ entry, and basal [Ca2+](i) in rat distal pulmonary arterial smooth muscle cells. Am J Physiol-Cell Ph. 2013;304:C833-C843.
Yu Y, Sweeney M, Zhang S, et al. PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating trpc6 expression. Am J Physiol Cell Physiol. 2003;284:C316-C330.
Yu Y, Keller SH, Remillard CV, et al. A functional single-nucleotide polymorphism in the TRPC6 gene promoter associated with idiopathic pulmonary arterial hypertension. Circulation. 2009;119:2313-2322.
Yamamura A, Yamamura H, Zeifman A, Yuan JX. Activity of Ca -activated cl channels contributes to regulating receptor- and store-operated ca entry in human pulmonary artery smooth muscle cells. Pulm Circ. 2011;1:269-279.
Lin MJ, Leung GP, Zhang WM, et al. Chronic hypoxia-induced upregulation of store-operated and receptor-operated Ca2+ channels in pulmonary arterial smooth muscle cells: a novel mechanism of hypoxic pulmonary hypertension. Circ Res. 2004;95:496-505.
Smith KA, Voiriot G, Tang H, et al. Notch activation of Ca(2+) signaling in the development of hypoxic pulmonary vasoconstriction and pulmonary hypertension. Am J Respir Cell Mol Biol. 2015;53:355-367.
Lu WJ, Ran PX, Zhang DD, et al. Sildenafil inhibits chronically hypoxic upregulation of canonical transient receptor potential expression in rat pulmonary arterial smooth muscle. Am J Physiol-Cell Ph. 2010;298:C114-C123.
Diez-Fraile A, Lammens T, Benoit Y, D'Herde KG. The calcium-sensing receptor as a regulator of cellular fate in normal and pathological conditions. Curr Mol Med. 2013;13:282-295.
Yamamura A, Guo Q, Yamamura H, et al. Enhanced Ca(2+)-sensing receptor function in idiopathic pulmonary arterial hypertension. Circ Res. 2012;111:469-481.
Chow JYC, Estrema C, Orneles T, Dong X, Barrett KE, Dong H. Calcium-sensing receptor modulates extracellular ca2+ entry via trpc-encoded receptor-operated channels in human aortic smooth muscle cells. Am J Physiol-Cell Ph. 2011;301:C461-C468.
Peng GY, Xu J, Liu RM, et al. Isolation, culture and identification of pulmonary arterial smooth muscle cells from rat distal pulmonary arteries. Cytotechnology. 2017;69:831-840.
Hong W, Peng G, Hao B, et al. Nicotine-induced airway smooth muscle cell proliferation involves trpc6-dependent calcium influx via alpha7 nachr. Cell Physiol Biochem. 2017;43:986-1002.
Salic A, Mitchison TJ. A chemical method for fast and sensitive detection of DNA synthesis in vivo. Proc Natl Acad Sci USA. 2008;105:2415-2420.
Peng G, Lu W, Li X, et al. Expression of store-operated ca2+ entry and transient receptor potential canonical and vanilloid-related proteins in rat distal pulmonary venous smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2010;299:L621-L630.
Peng G, Wang J, Lu W, Ran P. Isolation and primary culture of rat distal pulmonary venous smooth muscle cells. Hypertens Res. 2010;33:308-313.
Peng GY, Li SX, Hong W, et al. Chronic hypoxia increases intracellular ca2+ concentration via enhanced ca2+ entry through receptor-operated ca2+ channels in pulmonary venous smooth muscle cells. Circ J. 2015;79:2058-U2232.
Gan CT, Lankhaar JW, Westerhof N, et al. Noninvasively assessed pulmonary artery stiffness predicts mortality in pulmonary arterial hypertension. Chest. 2007;132:1906-1912.
Vanderpool RR, Kim AR, Molthen R, Chesler NC. Effects of acute rho kinase inhibition on chronic hypoxia-induced changes in proximal and distal pulmonary arterial structure and function. J Appl Physiol. 1985;2011(110):188-198.
Zhang H, Liu Y, Yan L, et al. Long noncoding rna hoxaas3 contributes to hypoxia-induced pulmonary artery smooth muscle cell proliferation. Cardiovasc Res. 2019;115:647-657.
Chen Y, Gao Y, Tao Y, Lin D, An S. Identification of a calcium-sensing receptor in human dental pulp cells that regulates mineral trioxide aggregate-induced mineralization. J Endod. 2019;45:907-916.
Wu M, Feng Y, Ye GX, et al. Calcium-sensing receptor activation attenuates collagen expression in renal proximal tubular epithelial cells. Am J Physiol Renal Physiol. 2019;316:F1006-F1015.
Conigrave AD, Ward DT. Calcium-sensing receptor (casr): pharmacological properties and signaling pathways. Best Pract Res Clin Endocrinol Metab. 2013;27:315-331.
Thomsen AR, Hvidtfeldt M, Brauner-Osborne H. Biased agonism of the calcium-sensing receptor. Cell Calcium. 2012;51:107-116.
Shibukawa Y, Suzuki T. Ca2+ signaling mediated by ip3-dependent ca2+ releasing and store-operated ca2+ channels in rat odontoblasts. J Bone Miner Res. 2003;18:30-38.
Thillaiappan NB, Chakraborty P, Hasan G, Taylor CW. Ip3 receptors and Ca(2+) entry. Biochim Biophys Acta Mol Cell Res. 2019;1866:1092-1100.
Chakraborty S, Deb BK, Chorna T, Konieczny V, Taylor CW, Hasan G. Mutant ip3 receptors attenuate store-operated Ca2+ entry by destabilizing stim-orai interactions in drosophila neurons. J Cell Sci. 2016;129:3903-3910.
Large WA, Saleh SN, Albert AP. Role of phosphoinositol 4,5-bisphosphate and diacylglycerol in regulating native trpc channel proteins in vascular smooth muscle. Cell Calcium. 2009;45:574-582.
Ramanathan G, Gupta S, Thielmann I, et al. Defective diacylglycerol-induced Ca2+ entry but normal agonist-induced activation responses in trpc6-deficient mouse platelets. J Thromb Haemost. 2012;10:419-429.
Lin MJ, Leung GPH, Zhang WM, et al. Chronic hypoxia-induced upregulation of store-operated and receptor-operated ca2+ channels in pulmonary arterial smooth muscle cells - a novel mechanism of hypoxic pulmonary hypertension. Circ Res. 2004;95:496-505.
Yang XR, Lin MJ, Sham JSK. Physiological functions of transient receptor potential channels in pulmonary arterial smooth muscle cells. Adv Exp Med Biol. 2010;661:109-122.
Malczyk M, Veith C, Fuchs B, et al. Classical transient receptor potential channel 1 in hypoxia-induced pulmonary hypertension. Am J Respir Crit Care Med. 2013;188:1451-1459.
Yang K, Lu W, Jia J, et al. Noggin inhibits hypoxia-induced proliferation by targeting store-operated calcium entry and transient receptor potential cation channels. Am J Physiol Cell Physiol. 2015;308:C869-C878.
Sun CK, Zhen YY, Lu HI, et al. Reducing trpc1 expression through liposome-mediated sirna delivery markedly attenuates hypoxia-induced pulmonary arterial hypertension in a murine model. Stem Cells Int. 2014;2014:316214.
Yamamura A, Nayeem MJ, Al Mamun A, Takahashi R, Hayashi H, Sato M. Platelet-derived growth factor up-regulates ca(2+)-sensing receptors in idiopathic pulmonary arterial hypertension. FASEB J. 2019;33:7363-7374.
Tang H, Yamamura A, Yamamura H, et al. Pathogenic role of calcium-sensing receptors in the development and progression of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2016;310:L846-L859.