{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:57:03Z","timestamp":1789390623847,"version":"build-2803163510"},"reference-count":64,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,19]],"date-time":"2021-09-19T00:00:00Z","timestamp":1632009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["08102003"],"award-info":[{"award-number":["08102003"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sleep apnea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]), and it is a known risk factor for hypertension. The upregulation of the renin-angiotensin system has been reported in IH, and the correlation between renin and CD38 has been noted. We exposed human HEK293 and mouse As4.1 renal cells to experimental IH or normoxia for 24 h and then measured the mRNA levels using a real-time reverse transcription polymerase chain reaction. The mRNA levels of Renin (Ren) and Cd38 were significantly increased by IH, indicating that they could be involved in the CD38-cyclic ADP-ribose signaling pathway. We next investigated the promotor activities of both genes, which were not increased by IH. Yet, a target mRNA search of the microRNA (miRNA) revealed both mRNAs to have a potential target sequence for miR-203. The miR-203 level of the IH-treated cells was significantly decreased when compared with the normoxia-treated cells. The IH-induced upregulation of the genes was abolished by the introduction of the miR-203 mimic, but not the miR-203 mimic NC negative control. These results indicate that IH stress downregulates the miR-203 in renin-producing cells, thereby resulting in increased mRNA levels of Ren and Cd38, which leads to hypertension.<\/jats:p>","DOI":"10.3390\/ijms221810127","type":"journal-article","created":{"date-parts":[[2021,9,21]],"date-time":"2021-09-21T08:04:23Z","timestamp":1632211463000},"page":"10127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Intermittent Hypoxia Upregulates the Renin and Cd38 mRNAs in Renin-Producing Cells via the Downregulation of miR-203"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7738-5576","authenticated-orcid":false,"given":"Yoshinori","family":"Takeda","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan"},{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asako","family":"Itaya-Hironaka","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9417-4738","authenticated-orcid":false,"given":"Akiyo","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumiyo","family":"Sakuramoto-Tsuchida","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyo","family":"Ota","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan"},{"name":"Respiratory Medicine, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuji","family":"Kawaguchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4066-0199","authenticated-orcid":false,"given":"Shin","family":"Takasawa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1848375","DOI":"10.1155\/2017\/1848375","article-title":"Review of and updates on hypertension in obstructive sleep apnea","volume":"2017","author":"Ahmad","year":"2017","journal-title":"Int. J. Hypertens."},{"key":"ref_2","first-page":"333","article-title":"Meta-analysis of effects of obstructive sleep apnea on the renin-angiotensin-aldosterone system","volume":"13","author":"Jin","year":"2016","journal-title":"J. Geriatr. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1161\/01.HYP.34.2.309","article-title":"Renin activity and blood pressure in response to chronic episodic hypoxia","volume":"34","author":"Fletcher","year":"1999","journal-title":"Hypertension"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11906-019-0995-y","article-title":"Potential contribution of carotid body-induced sympathetic and renin-angiotensin system overflow to pulmonary hypertension in intermittent hypoxia","volume":"21","author":"Iturriaga","year":"2019","journal-title":"Curr. Hypertens. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1159\/000343348","article-title":"Regulation of renin release via cyclic ADP-ribose-mediated signaling: Evidence from mice lacking CD38 gene","volume":"31","author":"Xiong","year":"2013","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1126\/science.1909457","article-title":"Ca2+-induced Ca2+ release in sea urchin egg homogenates: Modulation by cyclic ADP-ribose","volume":"253","author":"Galione","year":"1991","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1126\/science.8420005","article-title":"Cyclic ADP-ribose in insulin secretion from pancreatic \u03b2 cells","volume":"259","author":"Takasawa","year":"1993","journal-title":"Science"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1074\/jbc.273.5.2497","article-title":"Cyclic ADP-ribose and inositol 1,4,5-trisphosphate as alternate second messengers for intracellular Ca2+ mobilization in normal and diabetic \u03b2-cells","volume":"273","author":"Takasawa","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.bbrc.2010.05.051","article-title":"A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene","volume":"397","author":"Takasawa","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"26052","DOI":"10.1016\/S0021-9258(19)74275-6","article-title":"Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP","volume":"268","author":"Takasawa","year":"1993","journal-title":"J. Biol. Chem."},{"key":"ref_11","first-page":"79","article-title":"Pancreatic \u03b2-cell death, regeneration and insulin secretion: Roles of poly(ADP-ribose) polymerase and cyclic ADP-ribose","volume":"3","author":"Takasawa","year":"2002","journal-title":"Int. J. Exp. Diabetes Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Okamoto, H., and Takasawa, S. (2021). Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular Ca2+ mobilization and Reg ([Regenerating gene] protein)-Reg receptor system for cell regeneration. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci., 97, in press.","DOI":"10.2183\/pjab.97.022"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"S462","DOI":"10.2337\/diabetes.51.2007.S462","article-title":"Recent advances in the Okamoto model: The CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in \u03b2-cells","volume":"51","author":"Okamoto","year":"2002","journal-title":"Diabetes"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1159\/000100648","article-title":"Role of cyclic ADP-ribose-Ca2+ signaling in mediating renin production and release in As4.1 cells","volume":"19","author":"Yi","year":"2007","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1002\/cphy.c130040","article-title":"Classical renin-angiotensin system in kidney physiology","volume":"4","author":"Sparks","year":"2014","journal-title":"Compr. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"35599","DOI":"10.1074\/jbc.M112.392530","article-title":"Inhibition of cardiomyocytes differentiation of mouse embryonic stem cells by CD38\/cADPR\/Ca2+ signaling pathway","volume":"287","author":"Wei","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature11179","article-title":"Site-specific DICER and DROSHA RNA products control the DNA-damage response","volume":"488","author":"Francia","year":"2012","journal-title":"Nature"},{"key":"ref_18","first-page":"1702","article-title":"Dysregulation of microRNA biosynthesis enzyme Dicer plays an important role in gastric cancer progression","volume":"7","author":"Zhang","year":"2014","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"52.e1","DOI":"10.1016\/j.ajog.2013.07.033","article-title":"Maternal sleep-disordered breathing and adverse pregnancy outcomes: A systematic review and metaanalysis","volume":"210","author":"Pamidi","year":"2014","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1111\/jog.14362","article-title":"Nocturnal oxygen desaturation in the late third trimester of uncomplicated pregnancy for prediction of late-onset gestational hypertension","volume":"46","author":"Watanabe","year":"2020","journal-title":"J. Obstet. Gynaecol. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6982","DOI":"10.1038\/srep06982","article-title":"Obstructive sleep apnea and the risk of perinatal outcomes: A meta-analysis of cohort studies","volume":"4","author":"Xu","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1097\/AOG.0000000000001805","article-title":"Association between sleep-disordered breathing and hypertensive disorders of pregnancy and gestational diabetes mellitus","volume":"129","author":"Facco","year":"2017","journal-title":"Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s11325-018-1758-8","article-title":"Obstructive sleep apnea as a risk factor for preeclamsia-eclampsia","volume":"23","author":"Jaimchariyatam","year":"2019","journal-title":"Sleep Breath."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1161\/HYPERTENSIONAHA.110.152108","article-title":"Intermittent hypoxia increases arterial blood pressure in humans through a renin-angiotensin system-dependent mechanism","volume":"56","author":"Foster","year":"2010","journal-title":"Hypertension"},{"key":"ref_25","first-page":"R1105","article-title":"Acute hypoxia stimulates renin secretion and renin gene expression in vivo but not in vitro","volume":"272","author":"Ritthaler","year":"1997","journal-title":"Am. J. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"S155","DOI":"10.1046\/j.1523-1755.1998.06732.x","article-title":"Effects of hypoxia on renin secretion and renal renin gene expression","volume":"54","author":"Ritthaler","year":"1998","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/ndt\/15.1.11","article-title":"Effects of chronic hypoxia on renal renin gene expression in rats","volume":"15","author":"Schweda","year":"2000","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1093\/ajh\/hpu023","article-title":"Prevalence and associated factors of obstructive sleep apnea in patients with resistant hypertension","volume":"27","author":"Muxfeldt","year":"2014","journal-title":"Am. J. Hypertens."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1093\/sleep\/32.12.1589","article-title":"Obstructive sleep apnea and aldosterone","volume":"32","author":"Svatikova","year":"2009","journal-title":"Sleep"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1111\/jcmm.13076","article-title":"CD38 promotes angiotensin II-induced cardiac hypertrophy","volume":"21","author":"Guan","year":"2017","journal-title":"J. Cell. Mol. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1074\/jbc.M109.076216","article-title":"CD38-mediated Ca2+ signaling contributes to angiotensin II-induced activation of hepatic stellate cells: Attenuation of hepatic fibrosis by CD38 ablation","volume":"285","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/nrg3074","article-title":"Non-coding RNAs in human disease","volume":"12","author":"Esteller","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"42683","DOI":"10.18632\/oncotarget.7977","article-title":"MicroRNAs mediated regulation of MAPK signaling pathways in chronic myeloid leukemia","volume":"7","author":"Chakraborty","year":"2016","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"58595","DOI":"10.18632\/oncotarget.11193","article-title":"Anti-miR-203 suppresses ER-positive breast cancer growth and stemness by targeting SOCS3","volume":"7","author":"Muhammad","year":"2016","journal-title":"Oncotarget"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1002\/jcp.27160","article-title":"The potential prognostic and therapeutic application of tissue and circulating microRNAs in cervical cancer","volume":"234","author":"Hasanzadeh","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3389\/fgene.2019.00320","article-title":"Molecular mechanisms in clear cell renal cell carcinoma: Role of miRNAs and hypermethylated miRNA genes in crucial oncogenic pathways and processes","volume":"10","author":"Braga","year":"2019","journal-title":"Front. Genet."},{"key":"ref_37","first-page":"130","article-title":"Up-regulation of selenoprotein P and HIP\/PAP mRNAs in hepatocytes by intermittent hypoxia via down-regulation of miR-203","volume":"11","author":"Uchiyama","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.jacc.2015.06.1315","article-title":"Precision medicine in patients with resistant hypertension and obstructive sleep apnea: Blood pressure response to continuous positive airway pressure treatment","volume":"66","author":"Khalyfa","year":"2015","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_39","first-page":"8866","article-title":"Hypoxia is involved in hypoxic pulmonary hypertension through inhibiting the activation of FGF2 by miR-203","volume":"22","author":"Wang","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1007\/s00441-013-1741-4","article-title":"Expression of Ins1 and Ins2 genes in mouse fetal liver","volume":"355","author":"Takasawa","year":"2014","journal-title":"Cell Tissue Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.gene.2005.07.004","article-title":"Genomic organization, chromosomal localization, and promoter of human gene for FK506-binding protein 12.6","volume":"360","author":"Nakazawa","year":"2005","journal-title":"Gene"},{"key":"ref_42","first-page":"S5-004","article-title":"Intermittent hypoxia in pancreatic beta cells","volume":"5","author":"Ota","year":"2015","journal-title":"Pancreat. Disord. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.biocel.2017.12.012","article-title":"Up-regulation of POMC and CART mRNAs by intermittent hypoxia via GATA transcription factors in human neuronal cells","volume":"95","author":"Shobatake","year":"2018","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.lfs.2011.11.011","article-title":"Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38","volume":"90","author":"Ota","year":"2012","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Ota, H., Fujita, Y., Yamauchi, M., Muro, S., Kimura, H., and Takasawa, S. (2019). Relationship between intermittent hypoxia and Type 2 diabetes in sleep apnea syndrome. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194756"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Kimura, H., Ota, H., Kimura, Y., and Takasawa, S. (2019). Effects of intermittent hypoxia on pulmonary vascular and systemic diseases. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16173101"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1601731","DOI":"10.1183\/13993003.01731-2016","article-title":"Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation","volume":"49","author":"Murphy","year":"2017","journal-title":"Eur. Respir. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1016\/j.lfs.2013.09.001","article-title":"Pancreatic \u03b2 cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene","volume":"93","author":"Ota","year":"2013","journal-title":"Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1002\/2211-5463.12430","article-title":"Intermittent hypoxia-induced epiregulin expression by IL-6 production in human coronary artery smooth muscle cells","volume":"8","author":"Kyotani","year":"2018","journal-title":"FEBS Open Bio"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Shobatake, R., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Uchiyama, T., Ota, H., Takahashi, N., Ueno, S., and Sugie, K. (2019). Intermittent hypoxia up-regulates gene expressions of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and neurotensin (NTS) in enteroendocrine cells. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081849"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Uchiyama, T., Itaya-Hironaka, A., Yamauchi, A., Makino, M., Sakuramoto-Tsuchida, S., Shobatake, R., Ota, H., Takeda, M., Ohbayashi, C., and Takasawa, S. (2019). Intermittent hypoxia up-regulates CCL2, RETN, and TNF\u03b1 mRNAs in adipocytes via down-regulation of miR-452. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081960"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/cei.12142","article-title":"Involvement of autoimmunity to REG, a regeneration factor, in patients with primary Sj\u00f6gren\u2019s syndrome","volume":"174","author":"Yoshimoto","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"173058","DOI":"10.1155\/2015\/173058","article-title":"Synergistic activations of REG I\u03b1 and REG I\u03b2 promoters by IL-6 and glucocorticoids through JAK\/STAT pathway in human pancreatic \u03b2 cells","volume":"2015","author":"Yamauchi","year":"2015","journal-title":"J. Diabetes Res."},{"key":"ref_54","first-page":"69","article-title":"Interleukin-6\/STAT pathway is responsible for the induction of gene expression of REG I\u03b1, a new auto-antigen in Sj\u00f6gren\u05f3s syndrome patients, in salivary duct epithelial cells","volume":"2","author":"Fujimura","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_55","first-page":"123","article-title":"Human retinal pigment epithelial cell proliferation by the combined stimulation of hydroquinone and advanced glycation end-products via up-regulation of VEGF gene","volume":"2","author":"Tsujinaka","year":"2015","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_56","first-page":"198","article-title":"Expression of REG family genes in human inflammatory bowel diseases and its regulation","volume":"12","author":"Tsuchida","year":"2017","journal-title":"Biochem. Biophys. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Tohma, Y., Dohi, Y., Shobatake, R., Uchiyama, T., Takeda, M., Takasawa, S., Tanaka, Y., and Ohgushi, H. (2017). Reg gene expression in periosteum after fracture and its in vitro induction triggered by IL-6. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18112257"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1007\/s12026-019-9067-2","article-title":"Expression of human REG family genes in inflammatory bowel disease and their molecular mechanism","volume":"66","author":"Takasawa","year":"2018","journal-title":"Immunol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Akasaka, J., Naruse, K., Sado, T., Uchiyama, T., Makino, M., Yamauchi, A., Ota, H., Sakuramoto-Tsuchida, S., Itaya-Hironaka, A., and Takasawa, S. (2019). Involvement of receptor for advanced glycation endproducts in hypertensive disorders of pregnancy. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215462"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1074\/jbc.274.4.1869","article-title":"CD38 disruption impairs glucose-induced increases in cyclic ADP-ribose, [Ca2+]i, and insulin secretion","volume":"274","author":"Kato","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3111","DOI":"10.4049\/jimmunol.151.6.3111","article-title":"Expression cloning of a cDNA encoding a novel murine B cell activation marker. Homology to human CD38","volume":"151","author":"Harada","year":"1993","journal-title":"J. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1172\/JCI1656","article-title":"Autoantibodies against CD38 (ADP-ribosyl cyclase\/cyclic ADP-ribose hydrolase) that impair glucose-induced insulin secretion in noninsulin-dependent diabetes patients","volume":"102","author":"Ikehata","year":"1998","journal-title":"J. Clin. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1111\/j.1365-2362.2004.01419.x","article-title":"Autoantibodies to REG, a beta-cell regeneration factor, in diabetic patients","volume":"34","author":"Shervani","year":"2004","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1016\/j.bbamcr.2013.08.004","article-title":"Prevention of Reg I-induced \u03b2-cell apoptosis by IL-6\/dexamethasone through activation of HGF gene regulation","volume":"1833","author":"Nakagawa","year":"2013","journal-title":"Biochim. Biophys. Acta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/10127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:02:23Z","timestamp":1760166143000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/10127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,19]]},"references-count":64,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms221810127"],"URL":"https:\/\/doi.org\/10.3390\/ijms221810127","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,19]]}}}