{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T02:43:18Z","timestamp":1792291398077,"version":"4.4.0"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:p>\n                    Intracellular cAMP, the production of which is catalyzed by the\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -subunit of the stimulatory G protein (Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    ), controls renin synthesis and release by juxtaglomerular (JG) cells of the kidney, but may also have relevance for the physiologic integrity of the kidney. To investigate this possibility, we generated mice with inducible knockout of Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    in JG cells and monitored them for 6 months after induction at 6 weeks of age. The knockout mapped exclusively to the JG cells of the Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -deficient animals. Progressive albuminuria occurred in Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -deficient mice. Compared with controls expressing wild-type Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    alleles, the Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -deficient mice had enlarged glomeruli with mesangial expansion, injury, and FSGS at study end. Ultrastructurally, the glomerular filtration barrier of the Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    -deficient animals featured endothelial gaps, thickened basement membrane, and fibrin-like intraluminal deposits, which are classic signs of thrombotic microangiopathy. Additionally, we found endothelial damage in peritubular capillaries and vasa recta. Because deficiency of vascular endothelial growth factor (VEGF) results in thrombotic microangiopathy, we addressed the possibility that Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    knockout may result in impaired VEGF production. We detected VEGF expression in JG cells of control mice, and cAMP agonists regulated VEGF expression in cultured renin-producing cells. Our data demonstrate that Gs\n                    <jats:italic toggle=\"yes\">\u03b1<\/jats:italic>\n                    deficiency in JG cells of adult mice results in kidney injury, and suggest that JG cells are critically involved in the maintenance and protection of the renal microvascular endothelium.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017020173","type":"journal-article","created":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T20:25:26Z","timestamp":1501791926000},"page":"3479-3489","source":"Crossref","is-referenced-by-count":23,"title":["Interference with Gs\u03b1-Coupled Receptor Signaling in Renin-Producing Cells Leads to Renal Endothelial Damage"],"prefix":"10.1681","volume":"28","author":[{"given":"Peter","family":"Lachmann","sequence":"first","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Hickmann","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Steglich","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moath","family":"Al-Mekhlafi","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gerlach","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Jetschin","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Jahn","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Hamann","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, Dresden, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Wnuk","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Bern, Bern, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Renal Research, University of Southern Denmark, Odense, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Djonov","sequence":"additional","affiliation":[{"name":"Department of Anatomy, University of Bern, Bern, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee S.","family":"Weinstein","sequence":"additional","affiliation":[{"name":"Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Hohenstein","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian P.M.","family":"Hugo","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir T.","family":"Todorov","sequence":"additional","affiliation":[{"name":"Experimental Nephrology and Division of Nephrology, Department of Internal Medicine III and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,8,3]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1210\/edrv-13-3-536","article-title":"Receptor-effector coupling by G proteins: Implications for normal and abnormal signal transduction.","volume":"13","author":"Spiegel","year":"1992","journal-title":"Endocr Rev"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"5459","DOI":"10.1210\/en.2004-0865","article-title":"Minireview: GNAS: Normal and abnormal functions.","volume":"145","author":"Weinstein","year":"2004","journal-title":"Endocrinology"},{"key":"B3-20230819","first-page":"675","article-title":"Endocrine manifestations of stimulatory G protein alpha-subunit mutations and the role of genomic imprinting.","volume":"22","author":"Weinstein","year":"2001","journal-title":"Endocr Rev"},{"key":"B4-20230819","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1152\/physrev.00011.2009","article-title":"Physiology of kidney renin.","volume":"90","author":"Castrop","year":"2010","journal-title":"Physiol Rev"},{"key":"B5-20230819","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1152\/physrev.1990.70.4.1067","article-title":"Morphology, physiology, and molecular biology of renin secretion.","volume":"70","author":"Hackenthal","year":"1990","journal-title":"Physiol Rev"},{"key":"B6-20230819","doi-asserted-by":"crossref","first-page":"F27","DOI":"10.1152\/ajprenal.00193.2006","article-title":"Regulation of renin in mice with Cre recombinase-mediated deletion of G protein Gsalpha in juxtaglomerular cells.","volume":"292","author":"Chen","year":"2007","journal-title":"Am J Physiol Renal Physiol"},{"key":"B7-20230819","doi-asserted-by":"crossref","first-page":"F1006","DOI":"10.1152\/ajprenal.90448.2008","article-title":"Development of vascular renin expression in the kidney critically depends on the cyclic AMP pathway.","volume":"296","author":"Neubauer","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"B8-20230819","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000314635","article-title":"Renal failure in mice with Gsalpha deletion in juxtaglomerular cells.","volume":"32","author":"Chen","year":"2010","journal-title":"Am J Nephrol"},{"key":"B9-20230819","article-title":"Persistent and inducible neogenesis repopulates progenitor renin lineage cells in the kidney [published online ahead of print July 6, 2017]","author":"Hickmann","journal-title":"Kidney Int"},{"key":"B10-20230819","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1681\/ASN.2015080877","article-title":"Renin-angiotensin-aldosterone system inhibition increases podocyte derivation from cells of renin lineage.","volume":"27","author":"Lichtnekert","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B11-20230819","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1681\/ASN.2014030265","article-title":"Renin lineage cells repopulate the glomerular mesangium after injury.","volume":"26","author":"Starke","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B12-20230819","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1534-5807(04)00134-0","article-title":"Renin cells are precursors for multiple cell types that switch to the renin phenotype when homeostasis is threatened.","volume":"6","author":"Sequeira L\u00f3pez","year":"2004","journal-title":"Dev Cell"},{"key":"B13-20230819","doi-asserted-by":"crossref","first-page":"e134","DOI":"10.1093\/nar\/gnf134","article-title":"Stringent doxycycline dependent control of CRE recombinase in vivo.","volume":"30","author":"Sch\u00f6nig","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"B14-20230819","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/ki.2015.274","article-title":"Inducible glomerular erythropoietin production in the adult kidney.","volume":"88","author":"Gerl","year":"2015","journal-title":"Kidney Int"},{"key":"B15-20230819","doi-asserted-by":"crossref","first-page":"7386","DOI":"10.1073\/pnas.0408268102","article-title":"Alternative Gnas gene products have opposite effects on glucose and lipid metabolism.","volume":"102","author":"Chen","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B16-20230819","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/MNH.0b013e3283378f25","article-title":"Thrombotic microangiopathy: New insights.","volume":"19","author":"Benz","year":"2010","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"B17-20230819","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1681\/ASN.2015030321","article-title":"Extrarenal progenitor cells do not contribute to renal endothelial repair.","volume":"27","author":"Sradnick","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B18-20230819","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1056\/NEJMoa0707330","article-title":"VEGF inhibition and renal thrombotic microangiopathy.","volume":"358","author":"Eremina","year":"2008","journal-title":"N Engl J Med"},{"key":"B19-20230819","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1007\/s00424-011-0956-z","article-title":"cAMP target sequences enhCRE and CNRE sense low-salt intake to increase human renin gene expression in vivo.","volume":"461","author":"Desch","year":"2011","journal-title":"Pflugers Arch"},{"key":"B20-20230819","doi-asserted-by":"crossref","first-page":"2139","DOI":"10.1210\/me.2010-0134","article-title":"PPARgamma-dependent regulation of adenylate cyclase 6 amplifies the stimulatory effect of cAMP on renin gene expression.","volume":"24","author":"Desch","year":"2010","journal-title":"Mol Endocrinol"},{"key":"B21-20230819","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1681\/ASN.2006060633","article-title":"Pituitary adenylate cyclase-activating polypeptide stimulates renin secretion via activation of PAC1 receptors.","volume":"18","author":"Hautmann","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"B22-20230819","doi-asserted-by":"crossref","first-page":"R474","DOI":"10.1152\/ajpregu.00426.2003","article-title":"Ablation of renin-expressing juxtaglomerular cells results in a distinct kidney phenotype.","volume":"286","author":"Pentz","year":"2004","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B23-20230819","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1681\/ASN.2011080818","article-title":"Development of the renal arterioles.","volume":"22","author":"Sequeira Lopez","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B24-20230819","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1681\/ASN.2009090964","article-title":"The microRNA-processing enzyme dicer maintains juxtaglomerular cells.","volume":"21","author":"Sequeira-Lopez","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B25-20230819","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1681\/ASN.2004060490","article-title":"Ren1c homozygous null mice are hypotensive and polyuric, but heterozygotes are indistinguishable from wild-type.","volume":"16","author":"Takahashi","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"B26-20230819","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1074\/jbc.275.1.5","article-title":"Renin-dependent cardiovascular functions and renin-independent blood-brain barrier functions revealed by renin-deficient mice.","volume":"275","author":"Yanai","year":"2000","journal-title":"J Biol Chem"},{"key":"B27-20230819","first-page":"25","article-title":"Novel functions of renin precursors in homeostasis and disease.","volume":"31","author":"Gomez","year":"2016","journal-title":"Physiology (Bethesda)"},{"key":"B28-20230819","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1097\/MNH.0b013e32833aff32","article-title":"The renin phenotype: Roles and regulation in the kidney.","volume":"19","author":"Lopez","year":"2010","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"B29-20230819","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/sj.ki.5002571","article-title":"Development of renin expression in the mouse kidney.","volume":"73","author":"Sauter","year":"2008","journal-title":"Kidney Int"},{"key":"B30-20230819","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1203\/00006450-199611000-00002","article-title":"Mechanisms of proteinuria: Vascular permeability factor in congenital nephrotic syndrome of the Finnish type.","volume":"40","author":"Haltia","year":"1996","journal-title":"Pediatr Res"},{"key":"B31-20230819","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1681\/ASN.2011040401","article-title":"Genes that confer the identity of the renin cell.","volume":"22","author":"Brunskill","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B32-20230819","doi-asserted-by":"crossref","first-page":"29993","DOI":"10.1074\/jbc.M414530200","article-title":"Vascular endothelial growth factor induction by prostaglandin E2 in human airway smooth muscle cells is mediated by E prostanoid EP2\/EP4 receptors and SP-1 transcription factor binding sites.","volume":"280","author":"Bradbury","year":"2005","journal-title":"J Biol Chem"},{"key":"B33-20230819","doi-asserted-by":"crossref","first-page":"224","DOI":"10.4168\/aair.2013.5.4.224","article-title":"Effect of prostaglandin e2 on vascular endothelial growth factor production in nasal polyp fibroblasts.","volume":"5","author":"Han","year":"2013","journal-title":"Allergy Asthma Immunol Res"},{"key":"B34-20230819","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1161\/01.HYP.25.4.704","article-title":"Endogenous human renin expression and promoter activity in CALU-6, a pulmonary carcinoma cell line.","volume":"25","author":"Lang","year":"1995","journal-title":"Hypertension"},{"key":"B35-20230819","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1074\/jbc.272.4.2412","article-title":"Transactivation of the human renin promoter by the cyclic AMP\/protein kinase A pathway is mediated by both cAMP-responsive element binding protein-1 (CREB)-dependent and CREB-independent mechanisms in Calu-6 cells.","volume":"272","author":"Ying","year":"1997","journal-title":"J Biol Chem"},{"key":"B36-20230819","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1681\/ASN.2010030295","article-title":"Glomerular structure and function require paracrine, not autocrine, VEGF-VEGFR-2 signaling.","volume":"21","author":"Sison","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B37-20230819","doi-asserted-by":"crossref","first-page":"7963","DOI":"10.1073\/pnas.130192197","article-title":"Exploring the sequence space for tetracycline-dependent transcriptional activators: Novel mutations yield expanded range and sensitivity.","volume":"97","author":"Urlinger","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B38-20230819","doi-asserted-by":"crossref","first-page":"F783","DOI":"10.1152\/ajprenal.00279.2012","article-title":"Transcutaneous measurement of renal function in conscious mice.","volume":"303","author":"Schreiber","year":"2012","journal-title":"Am J Physiol Renal Physiol"},{"key":"B39-20230819","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1681\/ASN.2006050439","article-title":"P2Y1 gene deficiency protects from renal disease progression and capillary rarefaction during passive crescentic glomerulonephritis.","volume":"18","author":"Hohenstein","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"B40-20230819","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1161\/HYPERTENSIONAHA.109.138800","article-title":"Increased renin production in mice with deletion of peroxisome proliferator-activated receptor-gamma in juxtaglomerular cells.","volume":"55","author":"Desch","year":"2010","journal-title":"Hypertension"},{"key":"B41-20230819","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/ki.1991.175","article-title":"Role of growth hormone in the development of experimental renal scarring.","volume":"40","author":"el Nahas","year":"1991","journal-title":"Kidney Int"},{"key":"B42-20230819","doi-asserted-by":"crossref","first-page":"24483","DOI":"10.1074\/jbc.M111.329474","article-title":"Chicken ovalbumin upstream promoter transcription factor II regulates renin gene expression.","volume":"287","author":"Mayer","year":"2012","journal-title":"J Biol Chem"},{"key":"B43-20230819","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1161\/HYPERTENSIONAHA.107.092817","article-title":"Peroxisome proliferator-activated receptor-gamma is involved in the control of renin gene expression.","volume":"50","author":"Todorov","year":"2007","journal-title":"Hypertension"},{"key":"B44-20230819","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/ki.2009.418","article-title":"Inhibition of calcineurin phosphatase promotes exocytosis of renin from juxtaglomerular cells.","volume":"77","author":"Madsen","year":"2010","journal-title":"Kidney Int"},{"key":"B45-20230819","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1681\/ASN.2009010045","article-title":"Angiotensin II promotes development of the renal microcirculation through AT1 receptors.","volume":"21","author":"Madsen","year":"2010","journal-title":"J Am Soc Nephrol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201712000-00011","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:29:31Z","timestamp":1786130971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201712000-00011"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,3]]},"references-count":45,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2017020173","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,3]]}}}