{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:01:18Z","timestamp":1786132878861,"version":"build-2736575974"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,8]]},"abstract":"\n \n \n Chromogranin A (CHGA) is coreleased with catecholamines from secretory vesicles in adrenal medulla and sympathetic axons. Genetic variation in the\n CHGA<\/jats:italic>\n 3\u2032-region has been associated with autonomic control of circulation, hypertension, and hypertensive nephropathy, and the\n CHGA<\/jats:italic>\n 3\u2032-untranslated region (3\u2032-UTR) variant C+87T (rs7610) displayed peak associations with these traits in humans. Here, we explored the molecular mechanisms underlying these associations. C+87T occurred in a microRNA-107 (miR-107) motif (match: T>C), and\n CHGA<\/jats:italic>\n mRNA expression varied inversely with miR-107 abundance. In cells transfected with chimeric luciferase\/\n CHGA<\/jats:italic>\n 3\u2032-UTR reporters encoding either the T allele or the C allele, changes in miR-107 expression levels had much greater effects on expression of the T allele. Cotransfection experiments with hsa-miR-107 oligonucleotides and eukaryotic\n CHGA<\/jats:italic>\n plasmids produced similar results. Notably, an\n in vitro CHGA<\/jats:italic>\n transcription\/translation experiment revealed that changes in hsa-miR-107 expression altered expression of the T allele variant only. Mice with targeted ablation of\n Chga<\/jats:italic>\n exhibited greater eGFR. Using BAC transgenesis, we created a mouse model with a humanized\n CHGA<\/jats:italic>\n locus (T\/T genotype at C+87T), in which treatment with a hsa-miR-107 inhibitor yielded prolonged falls in SBP\/DBP compared with wild-type mice. We conclude that the\n CHGA<\/jats:italic>\n 3\u2032-UTR C+87T disrupts an miR-107 motif, with differential effects on\n CHGA<\/jats:italic>\n expression, and that a\n cis<\/jats:italic>\n :\n trans<\/jats:italic>\n (mRNA:miR) interaction regulates the association of\n CHGA<\/jats:italic>\n with BP and hypertensive nephropathy. These results indicate new strategies for probing autonomic circulatory control and ultimately, susceptibility to hypertensive renal sequelae.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2014060537","type":"journal-article","created":{"date-parts":[[2014,11,13]],"date-time":"2014-11-13T00:54:30Z","timestamp":1415840070000},"page":"1816-1825","source":"Crossref","is-referenced-by-count":18,"title":["Molecular Mechanism for Hypertensive Renal Disease"],"prefix":"10.1681","volume":"26","author":[{"given":"Kuixing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiful A.","family":"Mir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Makena","family":"Hightower","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Pablo","family":"Miramontes-Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam X.","family":"Maihofer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushil K.","family":"Mahata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline M.","family":"Nievergelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Schork","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry I.","family":"Freedman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sucheta M.","family":"Vaingankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T.","family":"O'Connor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-12-20240223","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1161\/01.CIR.101.3.329","article-title":"Essential hypertension. Part I: Definition and etiology.","volume":"101","author":"Carretero","year":"2000","journal-title":"Circulation"},{"key":"R2-12-20240223","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1056\/NEJMra021405","article-title":"The chromogranin-secretogranin family.","volume":"348","author":"Taupenot","year":"2003","journal-title":"N Engl J Med"},{"key":"R3-12-20240223","doi-asserted-by":"crossref","first-page":"1942","DOI":"10.1172\/JCI24354","article-title":"Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog.","volume":"115","author":"Mahapatra","year":"2005","journal-title":"J Clin Invest"},{"key":"R4-12-20240223","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/S0092-8674(01)00459-7","article-title":"Chromogranin A, an \u201con\/off\u201d switch controlling dense-core secretory granule biogenesis.","volume":"106","author":"Kim","year":"2001","journal-title":"Cell"},{"key":"R5-12-20240223","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1016\/S0021-9258(19)50695-0","article-title":"Calcium and catecholamine interactions with adrenal chromogranins. Comparison of driving forces in binding and aggregation.","volume":"267","author":"Videen","year":"1992","journal-title":"J Biol Chem"},{"key":"R6-12-20240223","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1172\/JCI119686","article-title":"Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist.","volume":"100","author":"Mahata","year":"1997","journal-title":"J Clin Invest"},{"key":"R7-12-20240223","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1038\/324476a0","article-title":"Pancreastatin, a novel pancreatic peptide that inhibits insulin secretion.","volume":"324","author":"Tatemoto","year":"1986","journal-title":"Nature"},{"key":"R8-12-20240223","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1111\/j.1463-1326.2006.00575.x","article-title":"Catecholamine storage vesicles and the metabolic syndrome: The role of the chromogranin A fragment pancreastatin.","volume":"8","author":"Zhang","year":"2006","journal-title":"Diabetes Obes Metab"},{"key":"R9-12-20240223","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/j.1365-2826.1993.tb00501.x","article-title":"Vasostatins, comprising the N-terminal domain of chromogranin A, suppress tension in isolated human blood vessel segments.","volume":"5","author":"Aardal","year":"1993","journal-title":"J Neuroendocrinol"},{"key":"R10-12-20240223","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1016\/j.jacc.2008.07.047","article-title":"Naturally occurring human genetic variation in the 3\u2032-untranslated region of the secretory protein chromogranin A is associated with autonomic blood pressure regulation and hypertension in a sex-dependent fashion.","volume":"52","author":"Chen","year":"2008","journal-title":"J Am Coll Cardiol"},{"key":"R11-12-20240223","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1681\/ASN.2007070754","article-title":"Chromogranin A polymorphisms are associated with hypertensive renal disease.","volume":"19","author":"Salem","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"R12-12-20240223","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1681\/ASN.2008111148","article-title":"Chromogranin A regulates renal function by triggering Weibel-Palade body exocytosis.","volume":"20","author":"Chen","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"R13-12-20240223","doi-asserted-by":"crossref","first-page":"41","DOI":"10.3109\/08860220903377597","article-title":"Common genetic variants in the chromogranin a promoter are associated with renal injury in IgA nephropathy patients with malignant hypertension.","volume":"32","author":"Yu","year":"2010","journal-title":"Ren Fail"},{"key":"R14-12-20240223","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1152\/physiolgenomics.00086.2009","article-title":"Long human CHGA flanking chromosome 14 sequence required for optimal BAC transgenic \u201crescue\u201d of disease phenotypes in the mouse Chga knockout.","volume":"41","author":"Vaingankar","year":"2010","journal-title":"Physiol Genomics"},{"key":"R15-12-20240223","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1097\/HJH.0b013e328336ed3e","article-title":"Effects of chromogranin A deficiency and excess in vivo: Biphasic blood pressure and catecholamine responses.","volume":"28","author":"Vaingankar","year":"2010","journal-title":"J Hypertens"},{"key":"R16-12-20240223","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1086\/381399","article-title":"Both rare and common polymorphisms contribute functional variation at CHGA, a regulator of catecholamine physiology.","volume":"74","author":"Wen","year":"2004","journal-title":"Am J Hum Genet"},{"key":"R17-12-20240223","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1161\/HYPERTENSIONAHA.106.081679","article-title":"Renal albumin excretion: Twin studies identify influences of heredity, environment, and adrenergic pathway polymorphism.","volume":"49","author":"Rao","year":"2007","journal-title":"Hypertension"},{"key":"R18-12-20240223","doi-asserted-by":"crossref","first-page":"13513","DOI":"10.1073\/pnas.0706217104","article-title":"A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance.","volume":"104","author":"Mishra","year":"2007","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R19-12-20240223","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.tig.2008.07.004","article-title":"MicroRNA target site polymorphisms and human disease.","volume":"24","author":"Sethupathy","year":"2008","journal-title":"Trends Genet"},{"key":"R20-12-20240223","doi-asserted-by":"crossref","first-page":"1452","DOI":"10.1038\/ng1910","article-title":"Natural selection on human microRNA binding sites inferred from SNP data.","volume":"38","author":"Chen","year":"2006","journal-title":"Nat Genet"},{"key":"R21-12-20240223","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/ki.1983.72","article-title":"Hemodynamically mediated glomerular injury and the progressive nature of kidney disease.","volume":"23","author":"Brenner","year":"1983","journal-title":"Kidney Int"},{"key":"R22-12-20240223","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1001\/jama.1990.03450210075036","article-title":"Glomerular hyperfiltration indicates early target organ damage in essential hypertension.","volume":"264","author":"Schmieder","year":"1990","journal-title":"JAMA"},{"key":"R23-12-20240223","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/01.HYP.24.6.752","article-title":"Renal hemodynamics in essential hypertension. Racial differences in response to changes in dietary sodium.","volume":"24","author":"Parmer","year":"1994","journal-title":"Hypertension"},{"key":"R24-12-20240223","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1006\/bbrc.1997.6782","article-title":"Novel quantitative trait loci for blood pressure and related traits on rat chromosomes 1, 10, and 18.","volume":"235","author":"Kov\u00e1cs","year":"1997","journal-title":"Biochem Biophys Res Commun"},{"key":"R25-12-20240223","doi-asserted-by":"crossref","first-page":"689","DOI":"10.33549\/physiolres.930000.52.689","article-title":"Gender-specific genetic determinants of blood pressure and organ weight: Pharmacogenetic approach.","volume":"52","author":"Ueno","year":"2003","journal-title":"Physiol Res"},{"key":"R26-12-20240223","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s00109-002-0394-7","article-title":"Resolving the composite trait of hypertension into its pharmacogenetic determinants by acute pharmacological modulation of blood pressure regulatory systems.","volume":"81","author":"Ueno","year":"2003","journal-title":"J Mol Med (Berl"},{"key":"R27-12-20240223","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1292\/jvms.64.45","article-title":"Detection of a quantitative trait locus for intramuscular fat accumulation using the OLETF rat.","volume":"64","author":"Tanomura","year":"2002","journal-title":"J Vet Med Sci"},{"key":"R28-12-20240223","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nature10112","article-title":"MicroRNAs 103 and 107 regulate insulin sensitivity.","volume":"474","author":"Trajkovski","year":"2011","journal-title":"Nature"},{"key":"R29-12-20240223","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1093\/cvr\/cvn155","article-title":"Catestatin is a novel endogenous peptide that regulates cardiac function and blood pressure.","volume":"80","author":"Mahapatra","year":"2008","journal-title":"Cardiovasc Res"},{"key":"R30-12-20240223","doi-asserted-by":"crossref","first-page":"28498","DOI":"10.1074\/jbc.M109.020636","article-title":"A novel pathway of insulin sensitivity in chromogranin A null mice: A crucial role for pancreastatin in glucose homeostasis.","volume":"284","author":"Gayen","year":"2009","journal-title":"J Biol Chem"},{"key":"R31-12-20240223","doi-asserted-by":"crossref","first-page":"e40323","DOI":"10.1371\/journal.pone.0040323","article-title":"MicroRNA 107 partly inhibits endothelial progenitor cells differentiation via HIF-1\u03b2.","volume":"7","author":"Meng","year":"2012","journal-title":"PLoS ONE"},{"key":"R32-12-20240223","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1093\/hmg\/ddt213","article-title":"MicroRNA-22 and promoter motif polymorphisms at the Chga locus in genetic hypertension: Functional and therapeutic implications for gene expression and the pathogenesis of hypertension.","volume":"22","author":"Friese","year":"2013","journal-title":"Hum Mol Genet"},{"key":"R33-12-20240223","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s11906-010-0170-y","article-title":"Catecholamine storage vesicles: Role of core protein genetic polymorphisms in hypertension.","volume":"13","author":"Zhang","year":"2011","journal-title":"Curr Hypertens Rep"},{"key":"R34-12-20240223","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/00004872-200207000-00020","article-title":"Early decline in the catecholamine release-inhibitory peptide catestatin in humans at genetic risk of hypertension.","volume":"20","author":"O\u2019Connor","year":"2002","journal-title":"J Hypertens"},{"key":"R35-12-20240223","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ymgme.2007.03.011","article-title":"Energizing miRNA research: A review of the role of miRNAs in lipid metabolism, with a prediction that miR-103\/107 regulates human metabolic pathways.","volume":"91","author":"Wilfred","year":"2007","journal-title":"Mol Genet Metab"},{"key":"R36-12-20240223","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1193032","article-title":"Association of trypanolytic ApoL1 variants with kidney disease in African Americans.","volume":"329","author":"Genovese","year":"2010","journal-title":"Science"},{"key":"R37-12-20240223","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta C(T)) method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"R38-12-20240223","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.cell.2007.04.040","article-title":"A mammalian microRNA expression atlas based on small RNA library sequencing.","volume":"129","author":"Landgraf","year":"2007","journal-title":"Cell"},{"key":"R39-12-20240223","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1111\/j.1523-1755.2004.00600.x","article-title":"Utility of endogenous creatinine clearance as a measure of renal function in mice.","volume":"65","author":"Dunn","year":"2004","journal-title":"Kidney Int"},{"key":"R40-12-20240223","doi-asserted-by":"crossref","first-page":"e363","DOI":"10.1371\/journal.pbio.0020363","article-title":"Human MicroRNA targets.","volume":"2","author":"John","year":"2004","journal-title":"PLoS Biol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201508000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:25:24Z","timestamp":1786130724000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201508000-00012"}},"subtitle":["Differential Regulation of Chromogranin A Expression at 3\u2032-Untranslated Region Polymorphism C+87T by MicroRNA-107"],"short-title":[],"issued":{"date-parts":[[2015,8]]},"references-count":40,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2014060537","relation":{},"ISSN":["1046-6673"],"issn-type":[{"value":"1046-6673","type":"print"}],"subject":[],"published":{"date-parts":[[2015,8]]}}}