TonEBP regulates the hyperosmotic expression of aquaporin 1 and 5 in the intervertebral disc.

Adult Animals Aquaporin 1 / genetics Aquaporin 5 / genetics Chondrocytes / metabolism Female Gene Expression Regulation Humans Intervertebral Disc Degeneration / genetics Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Nucleus Pulposus / metabolism Osmolar Concentration Primary Cell Culture RNA, Small Interfering / genetics Rats Rats, Wistar Signal Transduction Transcription Factors / antagonists & inhibitors

Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
04 02 2021
Historique:
received: 14 08 2020
accepted: 22 12 2020
entrez: 5 2 2021
pubmed: 6 2 2021
medline: 20 11 2021
Statut: epublish

Résumé

The central region of the intervertebral disc (IVD) is rich in proteoglycans, leading to a hyperosmotic environment, which fluctuates with daily loading. The cells of the nucleus pulposus (NP cells) have adapted to this environment via the function of tonicity enhancer binding protein (TonEBP), and NP cells have been shown to express several water channels known as aquaporins (AQP). We have previously shown that AQP1 and 5 decrease during IVD degeneration. Here, the regulation of AQP1 and 5 by hyperosmotic conditions and the role of TonEBP in this regulation was investigated. AQP1 and 5 gene expression was upregulated by hyperosmotic conditions mimicking the osmolality of the healthy IVD, which was abrogated by TonEBP knockdown. Furthermore, AQP1 and 5 immunopositivity was significantly reduced in TonEBP

Identifiants

DOI: 10.1038/s41598-021-81838-9 PMID: 33542263 PMC: PMC7862284
pubmed: 33542263
doi: 10.1038/s41598-021-81838-9
pii: 10.1038/s41598-021-81838-9
pmc: PMC7862284
doi:

Substances chimiques

AQP1 protein, human 0
AQP5 protein, human 0
Aquaporin 5 0
NFAT5 protein, human 0
Nfat5 protein, mouse 0
Nfat5 protein, rat 0
RNA, Small Interfering 0
Transcription Factors 0
Aquaporin 1 146410-94-8

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

3164

Subventions

Organisme : NIAMS NIH HHS
ID : R01 AR064733
Pays : United States

Références

Ishihara, H., Warensjo, K., Roberts, S. & Urban, J. P. Proteoglycan synthesis in the intervertebral disk nucleus: the role of extracellular osmolality. Am. J. Physiol. Physiol. 272, C1499–C1506 (1997).
doi: 10.1152/ajpcell.1997.272.5.C1499
Urban, J. P. G. The role of the physicochemical environment in determining disc cell behaviour. Biochem. Soc. Trans. 30, 858–864 (2002).
pubmed: 12440933 doi: 10.1042/bst0300858
McMillan, D. W., Garbutt, G. & Adams, M. A. Effect of sustained loading on the water content of intervertebral discs: implications for disc metabolism. Ann. Rheum. Dis. 55, 880–887 (1996).
pubmed: 9014581 pmcid: 1010338 doi: 10.1136/ard.55.12.880
Bibby, S. R. S., Jones, D. A., Ripley, R. M. & Urban, J. P. G. Metabolism of the intervertebral disc: effects of low levels of oxygen, glucose, and pH on rates of energy metabolism of bovine nucleus pulposus cells. Spine (Phila. Pa 1976) 30, 487–496 (2005).
doi: 10.1097/01.brs.0000154619.38122.47
Hartman, R. et al. Age-dependent changes in intervertebral disc cell mitochondria and bioenergetics. Eur. Cells Mater. 36, 171–183 (2018).
doi: 10.22203/eCM.v036a13
van Dijk, B., Potier, E. & Ito, K. Culturing bovine nucleus pulposus explants by balancing medium osmolarity. Tissue Eng. Part C Methods 17, 1089–1096 (2011).
pubmed: 21718168 doi: 10.1089/ten.tec.2011.0215
Johnson, Z. I., Shapiro, I. M. & Risbud, M. V. Extracellular osmolarity regulates matrix homeostasis in the intervertebral disc and articular cartilage: evolving role of TonEBP. Matrix Biol. 40, 10–16 (2014).
pubmed: 25172826 pmcid: 4390124 doi: 10.1016/j.matbio.2014.08.014
Neidlinger-Wilke, C. et al. Interactions of environmental conditions and mechanical loads have influence on matrix turnover by nucleus pulposus cells. J. Orthop. Res. 30, 112–121 (2012).
pubmed: 21674606 doi: 10.1002/jor.21481
O’Connell, G. D., Newman, I. B. & Carapezza, M. A. Effect of long-term osmotic loading culture on matrix synthesis from intervertebral disc cells. Bioresour. Open Access 3, 242–249 (2014).
doi: 10.1089/biores.2014.0021
Burg, M. B., Ferraris, J. D. & Dmitrieva, N. I. Cellular response to hyperosmotic stresses. Physiol. Rev. 87, 1441–1474 (2007).
pubmed: 17928589 doi: 10.1152/physrev.00056.2006
Macián, F., López-Rodríguez, C. & Rao, A. Partners in transcription: NFAT and AP-1. Oncogene 20, 2476–2489 (2001).
pubmed: 11402342 doi: 10.1038/sj.onc.1204386
Jauliac, S. et al. The role of NFAT transcription factors in integrin-mediated carcinoma invasion. Nat. Cell Biol. 4, 540–544 (2002).
pubmed: 12080349 doi: 10.1038/ncb816
Moeckel, G. W. et al. Role of integrin alpha1beta1 in the regulation of renal medullary osmolyte concentration. Am. J. Physiol. Renal Physiol. 290, F223–F231 (2006).
pubmed: 16106035 doi: 10.1152/ajprenal.00371.2004
Kino, T. et al. Brx mediates the response of lymphocytes to osmotic stress through the activation of NFAT5. Sci. Signal. 2, ra5 (2009).
pubmed: 19211510 pmcid: 2856329 doi: 10.1126/scisignal.2000081
Scherer, C. et al. Arterial wall stress controls NFAT5 activity in vascular smooth muscle cells. JAHA https://doi.org/10.1161/JAHA.113.000626 (2014).
doi: 10.1161/JAHA.113.000626 pubmed: 25074698 pmcid: 4310383
Miyakawa, H., Kyoon Woo, S., Dahl, S. C., Handler, J. S. & Moo Kwon, H. Tonicity-responsive enhancer binding protein, a Rel-like protein that stimulates transcription in response to hypertonicity. Physiology 96, 2538–2542 (1999).
Halterman, J. A., Kwon, H. M. & Wamhoff, B. R. Tonicity-independent regulation of the osmosensitive transcription factor TonEBP (NFAT5). Am. J. Physiol. Physiol. 302, C1–C8 (2012).
doi: 10.1152/ajpcell.00327.2011
Tsai, T.-T. et al. TonEBP/OREBP is a regulator of nucleus pulposus cell function and survival in the intervertebral disc. J. Biol. Chem. 281, 25416–25424 (2006).
pubmed: 16772300 doi: 10.1074/jbc.M601969200
Choi, H. et al. COX-2 expression mediated by calcium-TonEBP signaling axis under hyperosmotic conditions serves osmoprotective function in nucleus pulposus cells. J. Biol. Chem. 293, 8969–8981 (2018).
pubmed: 29700115 pmcid: 5995512 doi: 10.1074/jbc.RA117.001167
Hiyama, A. et al. Activation of TonEBP by calcium controls {beta}1,3-glucuronosyltransferase-I expression, a key regulator of glycosaminoglycan synthesis in cells of the intervertebral disc. J. Biol. Chem. 284, 9824–9834 (2009).
pubmed: 19147493 pmcid: 2665104 doi: 10.1074/jbc.M807081200
Tessier, S., Madhu, V., Johnson, Z. I., Shapiro, I. M. & Risbud, M. V. NFAT5/TonEBP controls early acquisition of notochord phenotypic markers, collagen composition, and sonic hedgehog signaling during mouse intervertebral disc embryogenesis. Dev. Biol. 455, 369–381 (2019).
pubmed: 31301300 pmcid: 6842424 doi: 10.1016/j.ydbio.2019.07.004
Tessier, S. et al. TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression. Matrix Biol. 87, 94–111 (2020).
pubmed: 31707045 doi: 10.1016/j.matbio.2019.10.007
Caron, M. M. J. et al. Osmolarity determines the in vitro chondrogenic differentiation capacity of progenitor cells via nuclear factor of activated T-cells 5. Bone 53, 94–102 (2013).
pubmed: 23219947 doi: 10.1016/j.bone.2012.11.032
Sadowska, A., Kameda, T., Krupkova, O. & Wuertz-Kozak, K. Osmosensing, osmosignalling and inflammation: how intervertebral disc cells respond to altered osmolarity. Eur. Cells Mater. 36, 231–250 (2018).
doi: 10.22203/eCM.v036a17
Kitchen, K. et al. Beyond water homeostasis: diverse functional roles of mammalian aquaporins. Biochim. Biophys. Acta 1850, 2410–2421 (2015).
pubmed: 26365508 doi: 10.1016/j.bbagen.2015.08.023
Varadaraj, K. & Kumari, S. S. Molecular mechanism of Aquaporin 0-induced fiber cell to fiber cell adhesion in the eye lens. Biochem. Biophys. Res. Commun. 506, 284–289 (2018).
pubmed: 30348525 pmcid: 6223623 doi: 10.1016/j.bbrc.2018.10.066
Papadopoulos, M. C., Saadoun, S. & Verkman, A. S. Aquaporins and cell migration. Pflügers Arch. Eur. J. Physiol. 456, 693–700 (2008).
doi: 10.1007/s00424-007-0357-5
Day, R. E. et al. Human aquaporins: regulators of transcellular water flow. Biochim. Biophys. Acta Gen. Subj. 1840, 1492–1506 (2014).
doi: 10.1016/j.bbagen.2013.09.033
Snuggs, J. W. et al. Aquaporin expression in the human and canine intervertebral disc during maturation and degeneration. JOR SPINE 2, e1049 (2019).
pubmed: 31463463 pmcid: 6686802 doi: 10.1002/jsp2.1049
Johnson, Z. I. et al. Aquaporin 1 and 5 expression decreases during human intervertebral disc degeneration: Novel HIF-1-mediated regulation of aquaporins in NP cells. Oncotarget 6, 11945–11958 (2015).
pubmed: 25844601 pmcid: 4494915 doi: 10.18632/oncotarget.3631
Richardson, S. M., Knowles, R., Marples, D., Hoyland, J. A. & Mobasheri, A. Aquaporin expression in the human intervertebral disc. J. Mol. Histol. 39, 303–309 (2008).
pubmed: 18247144 doi: 10.1007/s10735-008-9166-1
Jenq, W., Mathieson, I. M., Ihara, W. & Ramirez, G. Aquaporin-1: an osmoinducible water channel in cultured mIMCD-3 cells. Biochem. Biophys. Res. Commun. 245, 804–809 (1998).
pubmed: 9588195 doi: 10.1006/bbrc.1998.8518
Umenishi, F. & Schrier, R. W. Hypertonicity-induced aquaporin-1 (AQP1) expression is mediated by the activation of MAPK pathways and hypertonicity-responsive element in the AQP1 gene. J. Biol. Chem. 278, 15765–15770 (2003).
pubmed: 12600999 doi: 10.1074/jbc.M209980200
Lanaspa, M. A. et al. The expression of Aquaporin-1 in the Medulla Of The Kidney Is Dependent On The Transcription Factor Associated With Hypertonicity, TonEBP. J. Biol. Chem. 285, 31694–31703 (2010).
pubmed: 20639513 pmcid: 2951241 doi: 10.1074/jbc.M109.093690
Rutkovskiy, A. et al. Transient hyperosmolality modulates expression of cardiac aquaporins. Biochem. Biophys. Res. Commun. 425, 70–75 (2012).
pubmed: 22820194 doi: 10.1016/j.bbrc.2012.07.052
Chen, X., Zhou, C., Yan, C., Ma, J. & Zheng, W. Hyperosmotic stress induces cisplatin sensitivity in ovarian cancer cells by stimulating aquaporin-5 expression. Exp. Ther. Med. 10, 2055–2062 (2015).
pubmed: 26668595 pmcid: 4665691 doi: 10.3892/etm.2015.2833
Zhou, B. et al. Hypertonic induction of aquaporin-5: novel role of hypoxia-inducible factor-1α. Am. J. Physiol. Physiol. 292, C1280–C1290 (2007).
doi: 10.1152/ajpcell.00070.2006
Hollborn, M. et al. Regulation of the hyperosmotic induction of aquaporin 5 and VEGF in retinal pigment epithelial cells: involvement of NFAT5. Mol. Vis. 21, 360–377 (2015).
pubmed: 25878490 pmcid: 4390809
Gajghate, S. et al. Osmolarity and intracellular calcium regulate aquaporin2 expression through TonEBP in nucleus pulposus cells of the intervertebral disc. J. Bone Miner. Res. 24, 992–1001 (2009).
pubmed: 19138132 pmcid: 2683651 doi: 10.1359/jbmr.090103
Palacio-Mancheno, P. E., Evashwick-Rogler, T. W., Laudier, D. M., Purmessur, D. & Iatridis, J. C. Hyperosmolarity induces notochordal cell differentiation with aquaporin3 upregulation and reduced N-cadherin expression. J. Orthop. Res. 36, 788–798 (2018).
pubmed: 28853179
Fujita, N. et al. Expression of prolyl hydroxylases (PHDs) is selectively controlled by HIF-1 and HIF-2 proteins in nucleus pulposus cells of the intervertebral disc. J. Biol. Chem. 287, 16975–16986 (2012).
pubmed: 22451659 pmcid: 3351286 doi: 10.1074/jbc.M111.334466
Silagi, E. S. et al. Bicarbonate recycling by HIF-1-dependent carbonic anhydrase isoforms 9 and 12 is critical in maintaining intracellular pH and viability of nucleus pulposus cells. J. Bone Miner. Res. 33, 338–355 (2018).
pubmed: 28940640 doi: 10.1002/jbmr.3293
Wang, F. & Zhu, Y. Aquaporin-1: a potential membrane channel for facilitating the adaptability of rabbit nucleus pulposus cells to an extracellular matrix environment. J. Orthop. Sci. 16, 304–312 (2011).
pubmed: 21451971 doi: 10.1007/s00776-011-0055-1
Taş, U. et al. Aquaporin-1 and aquaporin-3 expressions in the intervertebral disc of rats with aging. Balkan Med. J. 29, 349–353 (2012).
pubmed: 25207032 pmcid: 4115877 doi: 10.5152/balkanmedj.2012.079
Muller, C., Sendler, M. & Hildebrandt, J.-P. Downregulation of aquaporins 1 and 5 in nasal gland by osmotic stress in ducklings, Anas platyrhynchos: implications for the production of hypertonic fluid. J. Exp. Biol. 209, 4067–4076 (2006).
pubmed: 17023601 doi: 10.1242/jeb.02491
Moon, Y., Hong, S. J., Shin, D. & Jung, Y. Increased aquaporin-1 expression in choroid plexus epithelium after systemic hyponatremia. Neurosci. Lett. 395, 1–6 (2006).
pubmed: 16293370 doi: 10.1016/j.neulet.2005.10.060
Esensten, J. H. et al. NFAT5 binds to the TNF promoter distinctly from NFATp, c, 3 and 4, and activates TNF transcription during hypertonic stress alone. Nucleic Acids Res. 33, 3845–3854. https://doi.org/10.1093/nar/gki701 (2005).
doi: 10.1093/nar/gki701 pubmed: 16027109 pmcid: 1175021
Ueno, M. et al. Fat-specific protein 27 modulates nuclear factor of activated T cells 5 and the cellular response to stress. J. Lipid Res. 54, 734–743 (2013).
pubmed: 23233732 pmcid: 3617947 doi: 10.1194/jlr.M033365
Küper, C., Beck, F.-X. & Neuhofer, W. NFAT5 contributes to osmolality-induced MCP-1 expression in mesothelial cells. Mediators Inflamm. 2012, 1–12 (2012).
doi: 10.1155/2012/513015
Le Maitre, C. L., Hoyland, J. A. & Freemont, A. J. Catabolic cytokine expression in degenerate and herniated human intervertebral discs: IL-1beta and TNFalpha expression profile. Arthritis Res. Ther. 9, R77 (2007).
pubmed: 17688691 pmcid: 2206382 doi: 10.1186/ar2275
Andrade, P. et al. Elevated IL-1β and IL-6 levels in lumbar herniated discs in patients with sciatic pain. Eur. Spine J. 22, 714–720 (2013).
pubmed: 23014739 doi: 10.1007/s00586-012-2502-x
Phillips, K. L. E. et al. Potential roles of cytokines and chemokines in human intervertebral disc degeneration: interleukin-1 is a master regulator of catabolic processes. Osteoarthr. Cartil. 23, 1165–1177 (2015).
doi: 10.1016/j.joca.2015.02.017
Johnson, Z. I. et al. TNF-α promotes nuclear enrichment of the transcription factor TonEBP/NFAT5 to selectively control inflammatory but not osmoregulatory responses in nucleus pulposus cells. J. Biol. Chem. 292, 17561–17575 (2017).
pubmed: 28842479 pmcid: 5655530 doi: 10.1074/jbc.M117.790378
Ozu, M., Galizia, L., Acuña, C. & Amodeo, G. Aquaporins: more than functional monomers in a tetrameric arrangement. Cells 7(11), 209. https://doi.org/10.3390/cells7110209 (2018).
doi: 10.3390/cells7110209 pmcid: 6262540
Benfenati, V. et al. An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. Proc. Natl. Acad. Sci. USA 108, 2563–2568 (2011).
pubmed: 21262839 doi: 10.1073/pnas.1012867108 pmcid: 3038710
Mola, M. G. et al. The speed of swelling kinetics modulates cell volume regulation and calcium signaling in astrocytes: a different point of view on the role of aquaporins. Glia 64, 139–154 (2016).
pubmed: 26413835 doi: 10.1002/glia.22921
Sive, J. I. et al. Expression of chondrocyte markers by cells of normal and degenerate intervertebral discs. J. Clin. Pathol. Mol. Pathol. 55, 91–97 (2002).
doi: 10.1136/mp.55.2.91
Le Maitre, C. L., Pockert, A., Buttle, D. J., Freemont, A. J. & Hoyland, J. A. Matrix synthesis and degradation in human intervertebral disc degeneration. Biochem. Soc. Trans. 35, 652–655 (2007).
pubmed: 17635113 doi: 10.1042/BST0350652
Le Maitre, C. L., Freemont, A. J. & Hoyland, J. A. Localization of degradative enzymes and their inhibitors in the degenerate human intervertebral disc. J. Pathol. 204, 47–54 (2004).
pubmed: 15307137 doi: 10.1002/path.1608
Go, W. Y., Liu, X., Roti, M. A., Liu, F. & Ho, S. N. NFATS/TonEBP mutant mice define osmotic stress as a critical feature of the lymphoid microenvironment. Proc. Natl. Acad. Sci. USA 101, 10673–10678 (2004).
pubmed: 15247420 doi: 10.1073/pnas.0403139101 pmcid: 489993
ImageJ. Available at: https://imagej.nih.gov/ij/ .

Auteurs

J W Snuggs (JW)

Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield, S1 1WB, UK.

S Tessier (S)

Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

R A B Bunning (RAB)

Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield, S1 1WB, UK.

I M Shapiro (IM)

Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Graduate Program in Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA.

M V Risbud (MV)

Department of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.
Graduate Program in Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA.

C L Le Maitre (CL)

Biomolecular Sciences Research Centre, Sheffield Hallam University, City Campus, Howard Street, Sheffield, S1 1WB, UK. C.Lemaitre@shu.ac.uk.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Eucaryotes › Animaux › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Porines › Aquaporines › Aquaporine-1 › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Canaux ioniques › Porines › Aquaporines › Aquaporine-5 › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Chondrocytes › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Maladies ostéomusculaires › Maladies osseuses › Maladies du rachis › Dégénérescence de disque intervertébral › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Souris knockout › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Tissus › Tissu conjonctif › Cartilage › Fibrocartilage › Disque intervertébral › Nucleus pulposus › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Phénomènes chimiques › Concentration osmolaire › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN non traduit › Petit ARN non traduit › Petit ARN interférent › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Wistar › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › TonEBP regulates the hyperosmotic expression...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › TonEBP regulates the hyperosmotic expression...