Skip to main content

Advertisement

SpringerLink
Log in

Stimulation of ORAI1 expression, store-operated Ca2+ entry, and osteogenic signaling by high glucose exposure of human aortic smooth muscle cells

  • Signaling and cell physiology
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Diabetes and chronic kidney disease (CKD) both trigger vascular osteogenic signaling and calcification leading to early death by cardiovascular events. Osteogenic signaling involves upregulation of the transcription factors CBFA1, MSX2, and SOX9, as well as alkaline phosphatase (ALP), an enzyme fostering calcification by degrading the calcification inhibitor pyrophosphate. In CKD, osteogenic signaling is triggered by hyperphosphatemia, which upregulates the serum and glucocorticoid-inducible kinase SGK1, a strong stimulator of the Ca2+-channel ORAI1. The channel is activated by STIM1 and accomplishes store-operated Ca2+-entry (SOCE). The present study explored whether exposure of human aortic smooth muscle cells (HAoSMCs) to high extracellular glucose concentrations similarly upregulates ORAI1 and/or STIM1 expression, SOCE, and osteogenic signaling. To this end, HAoSMCs were exposed to high extracellular glucose concentrations (15 mM, 24 h) without or with additional exposure to the phosphate donor ß-glycerophosphate. Transcript levels were estimated using qRT-PCR, protein abundance using Western blotting, ALP activity using a colorimetric assay kit, calcium deposits utilizing Alizarin red staining, cytosolic Ca2+-concentration ([Ca2+]i) by Fura-2-fluorescence, and SOCE from increase of [Ca2+]i following re-addition of extracellular Ca2+ after store depletion with thapsigargin (1 μM). As a result, glucose enhanced the transcript levels of SGK1 and ORAI1, ORAI2, and STIM2, protein abundance of ORAI1, SOCE, the transcript levels of CBFA1, MSX2, SOX9, and ALPL, as well as calcium deposits. Moreover, glucose significantly augmented the stimulating effect of ß-glycerophosphate on transcript levels of SGK1 and ORAI1, SOCE, the transcript levels of osteogenic markers, as well as calcium deposits. ORAI1 inhibitor MRS1845 (10 μM) significantly blunted the glucose-induced upregulation of the CBFA1 and MSX2 transcript levels. In conclusion, the hyperglycemia of diabetes stimulates expression of SGK1 and ORAI1, thus, augmenting store-operated Ca2+-entry and osteogenic signaling in HAoSMCs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Becchetti A, Arcangeli A (2010) Integrins and ion channels in cell migration: implications for neuronal development, wound healing and metastatic spread. Adv Exp Med Biol 674:107–123

    Article  CAS  Google Scholar 

  2. Bergmeier W, Weidinger C, Zee I, Feske S (2013) Emerging roles of store-operated Ca(2)(+) entry through STIM and ORAI proteins in immunity, hemostasis and cancer. Channels (Austin) 7:379–391. https://doi.org/10.4161/chan.24302

    Article  CAS  Google Scholar 

  3. Betjes MG (2013) Immune cell dysfunction and inflammation in end-stage renal disease. Nat Rev Nephrol 9:255–265. https://doi.org/10.1038/nrneph.2013.44

    Article  CAS  PubMed  Google Scholar 

  4. Blacher J, Guerin AP, Pannier B, Marchais SJ, London GM (2001) Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. Hypertension 38:938–942

    Article  CAS  Google Scholar 

  5. Burgoyne RD (2007) Neuronal calcium sensor proteins: generating diversity in neuronal Ca2+ signalling. Nat Rev Neurosci 8:182–193. https://doi.org/10.1038/nrn2093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Capiod T (2013) The need for calcium channels in cell proliferation. Recent Pat Anticancer Drug Discov 8:4–17

    Article  CAS  Google Scholar 

  7. Chaudhari S, Wu P, Wang Y, Ding Y, Yuan J, Begg M, Ma R (2014) High glucose and diabetes enhanced store-operated Ca(2+) entry and increased expression of its signaling proteins in mesangial cells. Am J Phys Renal Phys 306:F1069–F1080. https://doi.org/10.1152/ajprenal.00463.2013

    Article  CAS  Google Scholar 

  8. Cohen RA (1993) Dysfunction of vascular endothelium in diabetes mellitus. Circulation 87

  9. Courjaret R, Machaca K (2012) STIM and Orai in cellular proliferation and division. Front Biosci (Elite Ed) 4:331–341

    Article  Google Scholar 

  10. Fadini GP, Pauletto P, Avogaro A, Rattazzi M (2007) The good and the bad in the link between insulin resistance and vascular calcification. Atherosclerosis 193:241–244. https://doi.org/10.1016/j.atherosclerosis.2007.05.015

    Article  CAS  PubMed  Google Scholar 

  11. Fahrner M, Muik M, Derler I, Schindl R, Fritsch R, Frischauf I, Romanin C (2009) Mechanistic view on domains mediating STIM1-Orai coupling. Immunol Rev 231:99–112. https://doi.org/10.1111/j.1600-065X.2009.00815.x

    Article  PubMed  Google Scholar 

  12. Fleischhacker E, Esenabhalu VE, Spitaler M, Holzmann S, Skrabal F, Koidl B, Kostner GM, Graier WF (1999) Human diabetes is associated with hyperreactivity of vascular smooth muscle cells due to altered subcellular Ca2+ distribution. Diabetes 48:1323–1330. https://doi.org/10.2337/diabetes.48.6.1323

    Article  CAS  PubMed  Google Scholar 

  13. Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 32:S112–S119

    Article  CAS  Google Scholar 

  14. Graier WF, Posch K, Fleischhacker E, Wascher TC, Kostner GM (1999) Increased superoxide anion formation in endothelial cells during hyperglycemia: an adaptive response or initial step of vascular dysfunction? Diabetes Res Clin Pract 45:153–160. https://doi.org/10.1016/s0168-8227(99)00045-5

    Article  CAS  PubMed  Google Scholar 

  15. Graier WF, Posch K, Wascher TC, Kostner GM (1997) Role of superoxide anions in changes of endothelial vasoactive response during acute hyperglycemia. Horm Metab Res 29:622–626. https://doi.org/10.1055/s-2007-979113

    Article  CAS  PubMed  Google Scholar 

  16. Graier WF, Simecek S, Kukovetz WR, Kostner GM (1996) High D-glucose-induced changes in endothelial Ca2+/EDRF signaling are due to generation of superoxide anions. Diabetes 45:1386–1395. https://doi.org/10.2337/diab.45.10.1386

    Article  CAS  PubMed  Google Scholar 

  17. Graier WF, Wascher TC, Lackner L, Toplak H, Krejs GJ, Kukovetz WR (1993) Exposure to elevated D-glucose concentrations modulates vascular endothelial cell vasodilatory response. Diabetes 42:1497–1505. https://doi.org/10.2337/diab.42.10.1497

    Article  CAS  PubMed  Google Scholar 

  18. Haarhaus M, Brandenburg V, Kalantar-Zadeh K, Stenvinkel P, Magnusson P (2017) Alkaline phosphatase: a novel treatment target for cardiovascular disease in CKD. Nat Rev Nephrol 13:429–442. https://doi.org/10.1038/nrneph.2017.60

    Article  CAS  PubMed  Google Scholar 

  19. Hwang DY, Chien SC, Hsu YW, Kao CC, Cheng SY, Lu HC, Wu MS, Chang JM (2014) Genetic polymorphisms of ORAI1 and chronic kidney disease in Taiwanese population. Biomed Res Int 2014:290863–290866. https://doi.org/10.1155/2014/290863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jha JC, Ho F, Dan C, Jandeleit-Dahm K (2018) A causal link between oxidative stress and inflammation in cardiovascular and renal complications of diabetes. Clin Sci (Lond) 132:1811–1836. https://doi.org/10.1042/CS20171459

    Article  CAS  Google Scholar 

  21. Kappel S, Borgstrom A, Stoklosa P, Dorr K, Peinelt C (2019) Store-operated calcium entry in disease: beyond STIM/Orai expression levels. Semin Cell Dev Biol 94:66–73. https://doi.org/10.1016/j.semcdb.2019.01.003

    Article  CAS  PubMed  Google Scholar 

  22. Kapustin AN, Chatrou ML, Drozdov I, Zheng Y, Davidson SM, Soong D, Furmanik M, Sanchis P, De Rosales RT, Alvarez-Hernandez D, Shroff R, Yin X, Muller K, Skepper JN, Mayr M, Reutelingsperger CP, Chester A, Bertazzo S, Schurgers LJ, Shanahan CM (2015) Vascular smooth muscle cell calcification is mediated by regulated exosome secretion. Circ Res 116:1312–1323. https://doi.org/10.1161/CIRCRESAHA.116.305012

    Article  CAS  PubMed  Google Scholar 

  23. Lang F, Bohmer C, Palmada M, Seebohm G, Strutz-Seebohm N, Vallon V (2006) (Patho)physiological significance of the serum- and glucocorticoid-inducible kinase isoforms. Physiol Rev 86:1151–1178. https://doi.org/10.1152/physrev.00050.2005

    Article  CAS  PubMed  Google Scholar 

  24. Lang F, Eylenstein A, Shumilina E (2012) Regulation of Orai1/STIM1 by the kinases SGK1 and AMPK. Cell Calcium 52:347–354. https://doi.org/10.1016/j.ceca.2012.05.005

    Article  CAS  PubMed  Google Scholar 

  25. Lang F, Guelinckx I, Lemetais G, Melander O (2017) Two liters a day keep the doctor away? Considerations on the pathophysiology of suboptimal fluid intake in the common population. Kidney Blood Press Res 42:483–494. https://doi.org/10.1159/000479640

    Article  CAS  PubMed  Google Scholar 

  26. Lang F, Ritz E, Alesutan I, Voelkl J (2014) Impact of aldosterone on osteoinductive signaling and vascular calcification. Nephron Physiol 128:40–45. https://doi.org/10.1159/000368268

    Article  CAS  PubMed  Google Scholar 

  27. Lang F, Ritz E, Voelkl J, Alesutan I (2013) Vascular calcification--is aldosterone a culprit? Nephrol Dial Transplant 28:1080–1084. https://doi.org/10.1093/ndt/gft041

    Article  CAS  PubMed  Google Scholar 

  28. Lang F, Shumilina E (2013) Regulation of ion channels by the serum- and glucocorticoid-inducible kinase SGK1. FASEB J 27:3–12. https://doi.org/10.1096/fj.12-218230

    Article  CAS  PubMed  Google Scholar 

  29. London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731–1740

    Article  Google Scholar 

  30. Ma K, Liu P, Al-Maghout T, Sukkar B, Cao H, Voelkl J, Alesutan I, Pieske B, Lang F (2019) Phosphate-induced ORAI1 expression and store-operated Ca(2+) entry in aortic smooth muscle cells. J Mol Med 97:1465–1475. https://doi.org/10.1007/s00109-019-01824-7

    Article  CAS  PubMed  Google Scholar 

  31. Ma X, Chen Z, Wang L, Wang G, Wang Z, Dong X, Wen B, Zhang Z (2018) The pathogenesis of diabetes mellitus by oxidative stress and inflammation: its inhibition by berberine. Front Pharmacol 9:782. https://doi.org/10.3389/fphar.2018.00782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mizobuchi M, Towler D, Slatopolsky E (2009) Vascular calcification: the killer of patients with chronic kidney disease. J Am Soc Nephrol 20:1453–1464. https://doi.org/10.1681/ASN.2008070692

    Article  CAS  PubMed  Google Scholar 

  33. Moccia F, Dragoni S, Lodola F, Bonetti E, Bottino C, Guerra G, Laforenza U, Rosti V, Tanzi F (2012) Store-dependent Ca(2+) entry in endothelial progenitor cells as a perspective tool to enhance cell-based therapy and adverse tumour vascularization. Curr Med Chem 19:5802–5818

    Article  CAS  Google Scholar 

  34. Orrenius S, Zhivotovsky B, Nicotera P (2003) Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol 4:552–565. https://doi.org/10.1038/nrm1150

    Article  CAS  PubMed  Google Scholar 

  35. Peinelt C, Vig M, Koomoa DL, Beck A, Nadler MJ, Koblan-Huberson M, Lis A, Fleig A, Penner R, Kinet JP (2006) Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol 8:771–773. https://doi.org/10.1038/ncb1435

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Penna A, Demuro A, Yeromin AV, Zhang SL, Safrina O, Parker I, Cahalan MD (2008) The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers. Nature 456:116–120. https://doi.org/10.1038/nature07338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Prakriya M, Feske S, Gwack Y, Srikanth S, Rao A, Hogan PG (2006) Orai1 is an essential pore subunit of the CRAC channel. Nature 443:230–233. https://doi.org/10.1038/nature05122

    Article  CAS  PubMed  Google Scholar 

  38. Prevarskaya N, Skryma R, Shuba Y (2011) Calcium in tumour metastasis: new roles for known actors. Nat Rev Cancer 11:609–618. https://doi.org/10.1038/nrc3105

    Article  CAS  PubMed  Google Scholar 

  39. Putney JW Jr (2007) New molecular players in capacitative Ca2+ entry. J Cell Sci 120:1959–1965. https://doi.org/10.1242/jcs.03462

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Roderick HL, Cook SJ (2008) Ca2+ signalling checkpoints in cancer: remodelling Ca2+ for cancer cell proliferation and survival. Nat Rev Cancer 8:361–375. https://doi.org/10.1038/nrc2374

    Article  CAS  PubMed  Google Scholar 

  41. Sahu I, Pelzl L, Sukkar B, Fakhri H, Al-Maghout T, Cao H, Hauser S, Gutti R, Gawaz M, Lang F (2017) NFAT5-sensitive Orai1 expression and store-operated Ca(2+) entry in megakaryocytes. FASEB J 31:3439–3448. https://doi.org/10.1096/fj.201601211R

    Article  CAS  PubMed  Google Scholar 

  42. Salter RD, Watkins SC (2009) Dendritic cell altered states: what role for calcium? Immunol Rev 231:278–288. https://doi.org/10.1111/j.1600-065X.2009.00806.x

    Article  CAS  PubMed  Google Scholar 

  43. Samakai E, Hooper R, Soboloff J (2013) The critical role of STIM1-dependent Ca2+ signalling during T-cell development and activation. Int J Biochem Cell Biol 45:2491–2495. https://doi.org/10.1016/j.biocel.2013.07.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schmid E, Bhandaru M, Nurbaeva MK, Yang W, Szteyn K, Russo A, Leibrock C, Tyan L, Pearce D, Shumilina E, Lang F (2012) SGK3 regulates Ca(2+) entry and migration of dendritic cells. Cell Physiol Biochem 30:1423–1435. https://doi.org/10.1159/000343330

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Schmidt S, Liu G, Liu G, Yang W, Honisch S, Pantelakos S, Stournaras C, Honig A, Lang F (2014) Enhanced Orai1 and STIM1 expression as well as store operated Ca2+ entry in therapy resistant ovary carcinoma cells. Oncotarget 5:4799–4810. https://doi.org/10.18632/oncotarget.2035

    Article  PubMed  PubMed Central  Google Scholar 

  46. Shaw PJ, Feske S (2012) Regulation of lymphocyte function by ORAI and STIM proteins in infection and autoimmunity. J Physiol 590:4157–4167. https://doi.org/10.1113/jphysiol.2012.233221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Smyth JT, Hwang SY, Tomita T, DeHaven WI, Mercer JC, Putney JW (2010) Activation and regulation of store-operated calcium entry. J Cell Mol Med 14:2337–2349. https://doi.org/10.1111/j.1582-4934.2010.01168.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli CM (2001) Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 89:1147–1154

    Article  CAS  Google Scholar 

  49. Stengel B (2010) Chronic kidney disease and cancer: a troubling connection. J Nephrol 23:253–262

    PubMed  PubMed Central  Google Scholar 

  50. Tesfamariam B, Cohen RA (1992) Free radicals mediate endothelial cell dysfunction caused by elevated glucose. Am J Phys 263:H321–H326. https://doi.org/10.1152/ajpheart.1992.263.2.H321

    Article  CAS  Google Scholar 

  51. Tong X, Ying J, Pimentel DR, Trucillo M, Adachi T, Cohen RA (2008) High glucose oxidizes SERCA cysteine-674 and prevents inhibition by nitric oxide of smooth muscle cell migration. J Mol Cell Cardiol 44:361–369. https://doi.org/10.1016/j.yjmcc.2007.10.022

    Article  CAS  PubMed  Google Scholar 

  52. Towler DA, Shao JS, Cheng SL, Pingsterhaus JM, Loewy AP (2006) Osteogenic regulation of vascular calcification. Ann N Y Acad Sci 1068:327–333. https://doi.org/10.1196/annals.1346.036

    Article  CAS  PubMed  Google Scholar 

  53. Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science 312:1220–1223. https://doi.org/10.1126/science.1127883

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Voelkl J, Luong TT, Tuffaha R, Musculus K, Auer T, Lian X, Daniel C, Zickler D, Boehme B, Sacherer M, Metzler B, Kuhl D, Gollasch M, Amann K, Muller DN, Pieske B, Lang F, Alesutan I (2018) SGK1 induces vascular smooth muscle cell calcification through NF-kappaB signaling. J Clin Invest 128:3024–3040. https://doi.org/10.1172/JCI96477

    Article  PubMed  PubMed Central  Google Scholar 

  55. Waldegger S, Barth P, Raber G, Lang F (1997) Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume. Proc Natl Acad Sci U S A 94:4440–4445. https://doi.org/10.1073/pnas.94.9.4440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wang Y, Chaudhari S, Ren Y, Ma R (2015) Impairment of hepatic nuclear factor-4alpha binding to the Stim1 promoter contributes to high glucose-induced upregulation of STIM1 expression in glomerular mesangial cells. Am J Phys Renal Phys 308:F1135–F1145. https://doi.org/10.1152/ajprenal.00563.2014

    Article  CAS  Google Scholar 

  57. Warr C, Shaw K, Azim A, Piper M, Parsons L (2018) Using Mouse and Drosophila Models to Investigate the Mechanistic Links between Diet, Obesity, Type II Diabetes, and Cancer. 19:4110

  58. Wascher TC, Toplak H, Krejs GJ, Simecek S, Kukovetz WR, Graier WF (1994) Intracellular mechanisms involved in D-glucose-mediated amplification of agonist-induced Ca2+ response and EDRF formation in vascular endothelial cells. Diabetes 43:984–991. https://doi.org/10.2337/diab.43.8.984

    Article  CAS  PubMed  Google Scholar 

  59. Wu P, Ren Y, Ma Y, Wang Y, Jiang H, Chaudhari S, Davis ME, Zuckerman JE, Ma R (2017) Negative regulation of Smad1 pathway and collagen IV expression by store-operated Ca(2+) entry in glomerular mesangial cells. Am J Phys Renal Phys 312:F1090–F1100. https://doi.org/10.1152/ajprenal.00642.2016

    Article  CAS  Google Scholar 

  60. Wu P, Wang Y, Davis ME, Zuckerman JE, Chaudhari S, Begg M, Ma R (2015) Store-operated Ca2+ channels in mesangial cells inhibit matrix protein expression. J Am Soc Nephrol 26:2691–2702. https://doi.org/10.1681/ASN.2014090853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Yeromin AV, Zhang SL, Jiang W, Yu Y, Safrina O, Cahalan MD (2006) Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature 443:226–229. https://doi.org/10.1038/nature05108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Yuan T, Yang T, Chen H, Fu D, Hu Y, Wang J, Yuan Q, Yu H, Xu W, Xie X (2019) New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis. Redox Biol 20:247–260. https://doi.org/10.1016/j.redox.2018.09.025

    Article  CAS  PubMed  Google Scholar 

  63. Zhang SL, Kozak JA, Jiang W, Yeromin AV, Chen J, Yu Y, Penna A, Shen W, Chi V, Cahalan MD (2008) Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3. J Biol Chem 283:17662–17671. https://doi.org/10.1074/jbc.M801536200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zhang SL, Yu Y, Roos J, Kozak JA, Deerinck TJ, Ellisman MH, Stauderman KA, Cahalan MD (2005) STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437:902–905. https://doi.org/10.1038/nature04147

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhu X, Ma K, Zhou K, Voelkl J, Alesutan I, Leibrock C, Nurnberg B, Lang F (2020) Reversal of phosphate-induced ORAI1 expression, store-operated Ca(2+) entry and osteogenic signaling by MgCl2 in human aortic smooth muscle cells. Biochem Biophys Res Commun 523:18–24. https://doi.org/10.1016/j.bbrc.2019.11.005

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge the meticulous preparation of the manuscript by Lejla Subasic.

Funding

Xuexue Zhu, Kuo Zhou, and Hang Cao are supported by the Chinese Scholarship Council. Bernd Nürnberg is supported by the Deutsche Forschungsgemeinschaft (DFG; NU 53/12–2). The sponsor(s) had no role in study design, the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the article for publication.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Experimental Therapy & Toxicology, Eberhard-Karls-University of Tübingen, Tübingen, Germany

    Ke Ma, Basma Sukkar, Xuexue Zhu, Kuo Zhou, Hang Cao & Bernd Nürnberg

  2. Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Linz, Austria

    Jakob Voelkl & Ioana Alesutan

  3. DZHK (German Centre for Cardiovascular Research), partner site Berlin, Berlin, Germany

    Jakob Voelkl

  4. Department of Nephrology and Medical Intensive Care, Charité University Medicine, Berlin, Germany

    Jakob Voelkl

  5. Department of Molecular Medicine II, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

    Florian Lang

  6. Department of Physiology I, Eberhard-Karls-University of Tübingen, Tübingen, Germany

    Florian Lang

Authors
  1. Ke Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Basma Sukkar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xuexue Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kuo Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hang Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jakob Voelkl
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ioana Alesutan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bernd Nürnberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Florian Lang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

KM, BS, XZ, KZ, and HC performed experiments and analyzed data; FL, JV, IA, and BN designed research; FL drafted and wrote the manuscript. All authors corrected and approved the manuscript.

Corresponding author

Correspondence to Florian Lang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ma, K., Sukkar, B., Zhu, X. et al. Stimulation of ORAI1 expression, store-operated Ca2+ entry, and osteogenic signaling by high glucose exposure of human aortic smooth muscle cells. Pflugers Arch - Eur J Physiol 472, 1093–1102 (2020). https://doi.org/10.1007/s00424-020-02405-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-020-02405-1

Keywords

Search

Navigation