{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T20:02:36Z","timestamp":1762113756837,"version":"build-2065373602"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2018,9,27]],"date-time":"2018-09-27T00:00:00Z","timestamp":1538006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP16K08285"],"award-info":[{"award-number":["JP16K08285"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The up-regulated expression of the Ca2+-activated K+ channel KCa3.1 in inflammatory CD4+ T cells has been implicated in the pathogenesis of inflammatory bowel disease (IBD) through the enhanced production of inflammatory cytokines, such as interferon-\u03b3 (IFN-\u03b3). However, the underlying mechanisms have not yet been elucidated. The objective of the present study is to clarify the involvement of histone deacetylases (HDACs) in the up-regulation of KCa3.1 in the CD4+ T cells of IBD model mice. The expression levels of KCa3.1 and its regulators, such as function-modifying molecules and transcription factors, were quantitated using a real-time polymerase chain reaction (PCR) assay, Western blotting, and depolarization responses, which were induced by the selective KCa3.1 blocker TRAM-34 (1 \u03bcM) and were measured using a voltage-sensitive fluorescent dye imaging system. The treatment with 1 \u03bcM vorinostat, a pan-HDAC inhibitor, for 24 h repressed the transcriptional expression of KCa3.1 in the splenic CD4+ T cells of IBD model mice. Accordingly, TRAM-34-induced depolarization responses were significantly reduced. HDAC2 and HDAC3 were significantly up-regulated in the CD4+ T cells of IBD model mice. The down-regulated expression of KCa3.1 was observed following treatments with the selective inhibitors of HDAC2 and HDAC3. The KCa3.1 K+ channel regulates inflammatory cytokine production in CD4+ T cells, mediating epigenetic modifications by HDAC2 and HDAC3.<\/jats:p>","DOI":"10.3390\/ijms19102942","type":"journal-article","created":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T02:54:54Z","timestamp":1538103294000},"page":"2942","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Histone Deacetylases Enhance Ca2+-Activated K+ Channel KCa3.1 Expression in Murine Inflammatory CD4+ T Cells"],"prefix":"10.3390","volume":"19","author":[{"given":"Miki","family":"Matsui","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan"},{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Terasawa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Kajikuri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Kito","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyoko","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University, Kyoto 607-8414, Japan"},{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8471-1165","authenticated-orcid":false,"given":"Pattaporn","family":"Jaikhan","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 403-8334, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2439-879X","authenticated-orcid":false,"given":"Takayoshi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 403-8334, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5765-0667","authenticated-orcid":false,"given":"Susumu","family":"Ohya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Medical Sciences, Nagoya City University, Nagoya 467-8601, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2018,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/j.1600-065X.2009.00816.x","article-title":"The functional network of ion channels in T lymphocytes","volume":"231","author":"Cahalan","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1146\/annurev-immunol-032414-112212","article-title":"Ion channels in innate and adaptive immunity","volume":"33","author":"Feske","year":"2015","journal-title":"Annu. Rev. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/ddr.20467","article-title":"The lymphocyte potassium channels KV1.3 and KCa3.1 as targets for immunosuppression","volume":"72","author":"Lam","year":"2011","journal-title":"Drug Dev. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1248\/bpb.b18-00078","article-title":"Ca2+-activated K+ channel KCa3.1 as a therapeutic target for immune disorders","volume":"41","author":"Ohya","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1073\/pnas.0910133107","article-title":"Inhibition of the K+ channel KCa3.1 ameliorates T cell-mediated colitis","volume":"107","author":"Di","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","first-page":"B4946","article-title":"The role of T cell potassium channels, KV1.3 and KCa3.1, in the inflammatory cascade in ulcerative colitis","volume":"61","author":"Hansen","year":"2014","journal-title":"Dan. Med. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1111\/j.1476-5381.2012.02143.x","article-title":"NS6180, a new KCa3.1 channel inhibitor prevents T-cell activation and inflammation in a rat model of inflammatory bowel disease","volume":"168","author":"Brown","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"G873","DOI":"10.1152\/ajpgi.00156.2013","article-title":"Up-regulation of KCa3.1 K+ channel in mesenteric lymph node CD4+ T-lymphocytes from a mouse model of dextran sodium sulfate-induced inflammatory bowel disease","volume":"306","author":"Ohya","year":"2014","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zundler, S., Caioni, M., M\u00fcller, M., Strauch, U., Kunst, C., and Woelfel, G. (2016). K+ channel inhibition differentially regulates migration of intestinal epithelial cells in inflamed vs. non-inflamed conditions in a PI3K\/Akt-mediated manner. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147736"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"38765","DOI":"10.1074\/jbc.M110.168070","article-title":"Nucleoside diphosphate kinase B knock-out mice have impaired activation of the K+ channel KCa3.1, resulting in defective T cell activation","volume":"285","author":"Di","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3630","DOI":"10.1128\/MCB.25.9.3630-3638.2005","article-title":"The phosphatidylinositol 3-phosphate phosphatase myotubularin-related protein 6 (MTMR6) is a negative regulator of the Ca2+-activated K+ channel KCa3.1","volume":"25","author":"Srivastava","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.molcel.2006.11.012","article-title":"Histidine phosphorylation of the potassium channel KCa3.1 by nucleoside diphosphate kinase B is required for activation of KCa3.1 and CD4 T cells","volume":"24","author":"Srivastava","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"14442","DOI":"10.1073\/pnas.0803678105","article-title":"Protein histidine phosphatase 1 negatively regulates CD4 T cells by inhibiting the K+ channel KCa3.1","volume":"105","author":"Srivastava","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.molcel.2016.06.021","article-title":"Identification of PGAM5 as a mammalian protein histidine phosphatase that plays a central role to negatively regulate CD4+ T cells","volume":"63","author":"Panda","year":"2016","journal-title":"Mol. Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1074\/jbc.M003941200","article-title":"Up-regulation of the IKCa1 potassium channel during T-cell activation. Molecular mechanism and functional consequences","volume":"275","author":"Ghanshani","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1016\/j.bcp.2013.02.032","article-title":"Angiotensin II upregulates KCa3.1 channels and stimulates cell proliferation in rat cardiac fibroblasts","volume":"85","author":"Wang","year":"2013","journal-title":"Biochem. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gole, H.K., Tharp, D.L., and Bowles, D.K. (2014). Upregulation of intermediate-conductance Ca2+-activated K+ channels (KCNN4) in porcine coronary smooth muscle requires NADPH oxidase 5 (NOX5). PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0105337"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.3389\/fncel.2014.00183","article-title":"IL-4 type 1 receptor signaling up-regulates KCNN4 expression, and increases the KCa3.1 current and its contribution to migration of alternative-activated microglia","volume":"8","author":"Ferreira","year":"2014","journal-title":"Front. Cell Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molcel.2005.08.030","article-title":"Downregulated REST transcription factor is a switch enabling critical potassium channel expression and cell proliferation","volume":"20","author":"Cheong","year":"2005","journal-title":"Mol. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1124\/jpet.111.182782","article-title":"Intermediate-conductance Ca2+-activated K+ channel, KCa3.1, as a novel therapeutic target for benign prostatic hyperplasia","volume":"338","author":"Ohya","year":"2011","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e00228","DOI":"10.1002\/prp2.228","article-title":"Downregulation of the Ca2+-activated K+ channel KCa3.1 by histone deacetylase inhibition in human breast cancer cells","volume":"4","author":"Ohya","year":"2016","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"426","DOI":"10.2119\/molmed.2011.00069","article-title":"Inhibition of histone deacetylases in inflammatory bowel diseases","volume":"17","author":"Glauben","year":"2011","journal-title":"Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1267\/ahc.17033","article-title":"The HDAC inhibitor, SAHA, prevents colonic inflammation by suppressing pro-inflammatory cytokines and chemokines in DSS-induced colitis","volume":"51","author":"Ali","year":"2018","journal-title":"Acta Histochem. Cytochem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1476-9255-8-1","article-title":"Differential patterns of histone acetylation in inflammatory bowel diseases","volume":"8","author":"Tsaprouni","year":"2011","journal-title":"J. Inflamm. (Lond.)"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1053\/j.gastro.2009.10.037","article-title":"Inhibition of HDAC9 increases T regulatory cell function and prevents colitis in mice","volume":"138","author":"Wang","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/mi.2014.10","article-title":"Targeting surtuin-1 alleviates experimental autoimmune colitis by induction of Foxp3+ T-regulatory cells","volume":"7","author":"Akimova","year":"2014","journal-title":"Mucosal Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1172\/JCI77088","article-title":"FOXP3+ regulatory T cell development and function require histone\/protein deacetylase 3","volume":"125","author":"Wang","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1111\/apt.13008","article-title":"Review article: Selective histone deacetylase isoforms as potential therapeutic targets in inflammatory bowel diseases","volume":"41","author":"Felice","year":"2015","journal-title":"Aliment Pharmacol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"7499","DOI":"10.1016\/S0021-9258(18)32205-1","article-title":"A role of valency of concanavalin A and its chemically modified derivatives in lymphocyte activation. Monovalent monomeric concanavalin A derivative can stimulate lymphocyte blastoid transformation","volume":"258","author":"Saito","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.jphs.2016.10.007","article-title":"Defective splicing of the background K+ channel K2P5.1 by the pre-mRNA splicing inhibitor, pladienolide B in lectin-activated mouse splenic CD4+ T cells","volume":"132","author":"Tagishi","year":"2016","journal-title":"J. Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.bmcl.2007.12.031","article-title":"Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1\/HDAC2 inhibitors (SHI-1:2)","volume":"18","author":"Methot","year":"2008","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Suzuki, T., Kasuya, Y., Itoh, Y., Ota, Y., Zhan, P., Asamitsu, K., Nakagawa, H., Okamoto, T., and Miyata, N. (2013). Identification of highly selective and potent histone deacetylase 3 inhibitors using click chemistry-based combinatorial fragment assembly. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068669"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1124\/jpet.114.217315","article-title":"Downregulation of Ca2+-activated Cl\u2212 channel TMEM16A by the inhibition of histone deacetylase in TMEM16A-expressing cancer cells","volume":"351","author":"Matsuba","year":"2014","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1042\/BST0391092","article-title":"Histone deacetylase inhibitors and their potential role in inflammatory bowel diseases","volume":"39","author":"Edwards","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1248\/bpb.b16-01023","article-title":"A high potent and selective histone deacetylase 6 inhibitor prevents DSS-induced colitis in mice","volume":"40","author":"Liu","year":"2017","journal-title":"Biol. Pharm. Bull."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/labinvest.2008.38","article-title":"Decoy oligodeoxynucleotide targeting activator protein-1 (AP-1) attenuates intestinal inflammation in murine experimental colitis","volume":"88","author":"Moriyama","year":"2008","journal-title":"Lab. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Costello, C.M., Mah, N., H\u00e4sler, R., Rosenstiel, P., Waetzig, G.H., Hahn, A., Lu, T., Gurbuz, Y., Nikolaus, S., and Albrecht, M. (2005). Dissection of the inflammatory bowel disease transcriptome using genome-wide cDNA microarrays. PLoS Med., 2.","DOI":"10.1371\/journal.pmed.0020199"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1177\/1535370218769420","article-title":"The effects of dihydroartemisinin on inflammatory bowel disease-related bone loss in a rat model","volume":"243","author":"Ge","year":"2018","journal-title":"Exp. Biol. Med. (Maywood)"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1007\/BF02213120","article-title":"Expression of protooncogene-encoded mRNA by colonic epithelial cells in inflammatory bowel disease","volume":"41","author":"Alexander","year":"1996","journal-title":"Dig. Dis. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1124\/jpet.116.236711","article-title":"An HDAC6 inhibitor confers protection and selectivity inhibits B-cell infiltration in DSS-induced colitis in mice","volume":"360","author":"Do","year":"2017","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2893","DOI":"10.3892\/mmr.2017.6912","article-title":"Analysis of murine and human Treg subsets in inflammatory bowel disease","volume":"16","author":"Sun","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/art.33382","article-title":"Histone deacetylases are dysregulated in rheumatoid arthritis and a novel histone deacetylase 3-selective inhibitor reduces interleukin-6 production by peripheral blood mononuclear cells from rheumatoid arthritis patients","volume":"64","author":"Gillespie","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1183\/09031936.05.00117504","article-title":"Histone acetylation and deacetylation: Important in inflammatory lung disease","volume":"25","author":"Barnes","year":"2005","journal-title":"Eur. Respir. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"45047","DOI":"10.1038\/srep45047","article-title":"HDAC1-3 inhibitor MS-275 enhances IL10 expression in RAW264.7 macrophages and reduces cigarette smoke-induced airway inflammation in mice","volume":"7","author":"Leus","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.bcp.2016.03.010","article-title":"HDAC3-selective inhibitor RGFP966 demonstrates anti-inflammatory properties in RAW 264.7 macrophages and mouse precision-cut lung slides by attenuating NF-\u03baB p65 transcriptional activity","volume":"106","author":"Leus","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.atherosclerosis.2014.12.048","article-title":"Histone deacetylases and atherosclerosis","volume":"240","author":"Zheng","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.15252\/emmm.201404170","article-title":"Targeting macrophage histone deacetylase 3 stabilizes atherosclerotic lesions","volume":"6","author":"Hoeksema","year":"2014","journal-title":"EMBO Mol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"F729","DOI":"10.1152\/ajprenal.00086.2009","article-title":"Histone deacetylase-2 is a key regulator of diabetes- and transforming growth factor-beta1-induced renal injury","volume":"297","author":"Noh","year":"2009","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.taap.2016.07.003","article-title":"Role of histone deacetylases (HDACs) in progression and reversal of liver fibrosis","volume":"306","author":"Li","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2923","DOI":"10.2337\/db13-0135","article-title":"Blockade of KCa3.1 ameliorates renal fibrosis through the TGF-\u03b21\/Smad pathway in diabetic mice","volume":"62","author":"Huang","year":"2013","journal-title":"Diabetes"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"23884","DOI":"10.1038\/srep23884","article-title":"KCa3.1 mediates dysfunction of tubular autophagy in diabetic kidneys via PI3k\/Akt\/mTOR signaling pathways","volume":"6","author":"Huang","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Anumanthan, G., Gupta, S., Fink, M.K., Hesemann, N.P., Bowles, D.K., McDaniel, L.M., Muhammad, M., and Mohan, R.R. (2018). KCa3.1 ion channel: A novel therapeutic target for corneal fibrosis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192145"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1165\/rcmb.2016-0092OC","article-title":"Inhibition of the KCa3.1 channel alleviates established pulmonary fibrosis in a large animal model","volume":"56","author":"Organ","year":"2017","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1165\/rcmb.2012-0236OC","article-title":"Targeted inhibition of KCa3.1 channel attenuates airway inflammation and remodeling in allergic asthma","volume":"48","author":"Yu","year":"2013","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.pharmthera.2016.02.001","article-title":"Recent advances in therapeutic strategies that focus on the regulation of ion channel expression","volume":"160","author":"Ohya","year":"2016","journal-title":"Pharmacol. Ther."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/2942\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:22:45Z","timestamp":1760196165000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/19\/10\/2942"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,27]]},"references-count":55,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2018,10]]}},"alternative-id":["ijms19102942"],"URL":"https:\/\/doi.org\/10.3390\/ijms19102942","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2018,9,27]]}}}