{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T23:24:40Z","timestamp":1774481080133,"version":"3.50.1"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T00:00:00Z","timestamp":1503014400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,8,18]],"date-time":"2017-08-18T00:00:00Z","timestamp":1503014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Chronic inflammation can be a major driver of the failure of a variety of organs, including chronic kidney disease (CKD). The NLR family pyrin domain-containing 3 (NLRP3) inflammasome has been shown to play a pivotal role in inflammation in a mouse kidney disease model. Nuclear factor erythroid 2-related factor 2 (Nrf2), the master transcription factor for anti-oxidant responses, has also been implicated in inflammasome activation under physiological conditions. However, the mechanism underlying inflammasome activation in CKD remains elusive. Here, we show that the loss of Nrf2 suppresses fibrosis and inflammation in a unilateral ureter obstruction (UUO) model of CKD in mice. We consistently observed decreased expression of inflammation-related genes <jats:italic>NLRP3<\/jats:italic> and <jats:italic>IL-1\u03b2<\/jats:italic> in <jats:italic>Nrf2<\/jats:italic>-deficient kidneys after UUO. Increased infiltration of M1, but not M2, macrophages appears to mediate the suppression of UUO-induced CKD symptoms. Furthermore, we found that activation of the NLRP3 inflammasome is attenuated in <jats:italic>Nrf2<\/jats:italic>-deficient bone marrow\u2013derived macrophages. These results demonstrate that Nrf2-related inflammasome activation can promote CKD symptoms via infiltration of M1 macrophages. Thus, we have identified the Nrf2 pathway as a promising therapeutic target for CKD.<\/jats:p>","DOI":"10.1038\/s41598-017-08054-2","type":"journal-article","created":{"date-parts":[[2017,8,14]],"date-time":"2017-08-14T14:11:41Z","timestamp":1502719901000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Infiltration of M1, but not M2, macrophages is impaired after unilateral ureter obstruction in Nrf2-deficient mice"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6641-3030","authenticated-orcid":false,"given":"Yuji","family":"Sogawa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hajime","family":"Nagasu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2280-7422","authenticated-orcid":false,"given":"Shigeki","family":"Iwase","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chieko","family":"Ihoriya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Itano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Uchida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kengo","family":"Kidokoro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shun\u2019ichiro","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minoru","family":"Satoh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tamaki","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takafumi","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masayuki","family":"Yamamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Horng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Kashihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,18]]},"reference":[{"key":"8054_CR1","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1111\/j.1745-7254.2007.00688.x","volume":"28","author":"MS Yates","year":"2007","unstructured":"Yates, M. S. & Kensler, T. W. Keap1 eye on the target: chemoprevention of liver cancer. Acta Pharmacol Sin \n                           28, 1331\u20131342 (2007).","journal-title":"Acta Pharmacol Sin"},{"key":"8054_CR2","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1146\/annurev-pharmtox-011112-140320","volume":"53","author":"Q Ma","year":"2013","unstructured":"Ma, Q. Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol \n                           53, 401\u2013426 (2013).","journal-title":"Annu Rev Pharmacol Toxicol"},{"key":"8054_CR3","doi-asserted-by":"publisher","first-page":"26190","DOI":"10.1074\/jbc.M109.095786","volume":"285","author":"S Seng","year":"2010","unstructured":"Seng, S., Avraham, H. K., Birrane, G., Jiang, S. & Avraham, S. Nuclear matrix protein (NRP\/B) modulates the nuclear factor (Erythroid-derived 2)-related 2 (NRF2)-dependent oxidative stress response. J Biol Chem \n                           285, 26190\u201326198 (2010).","journal-title":"J Biol Chem"},{"key":"8054_CR4","doi-asserted-by":"publisher","first-page":"e0125726","DOI":"10.1371\/journal.pone.0125726","volume":"10","author":"CC Wu","year":"2015","unstructured":"Wu, C. C. et al. Resveratrol ameliorates renal damage, increases expression of heme oxygenase-1, and has anti-complement, anti-oxidative, and anti-apoptotic effects in a murine model of membranous nephropathy. PLoS One \n                           10, e0125726 (2015).","journal-title":"PLoS One"},{"key":"8054_CR5","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/j.freeradbiomed.2013.03.024","volume":"61","author":"SM Yang","year":"2013","unstructured":"Yang, S. M. et al. Antroquinonol mitigates an accelerated and progressive IgA nephropathy model in mice by activating the Nrf2 pathway and inhibiting T cells and NLRP3 inflammasome. Free Radic Biol Med \n                           61, 285\u2013297 (2013).","journal-title":"Free Radic Biol Med"},{"key":"8054_CR6","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/j.freeradbiomed.2016.01.011","volume":"92","author":"T Qin","year":"2016","unstructured":"Qin, T. et al. Sinomenine activation of Nrf2 signaling prevents hyperactive inflammation and kidney injury in a mouse model of obstructive nephropathy. Free Radic Biol Med \n                           92, 90\u201399 (2016).","journal-title":"Free Radic Biol Med"},{"key":"8054_CR7","doi-asserted-by":"publisher","first-page":"17020","DOI":"10.1074\/jbc.M114.563114","volume":"289","author":"C Zhao","year":"2014","unstructured":"Zhao, C., Gillette, D. D., Li, X., Zhang, Z. & Wen, H. Nuclear factor E2-related factor-2 (Nrf2) is required for NLRP3 and AIM2 inflammasome activation. J Biol Chem \n                           289, 17020\u201317029 (2014).","journal-title":"J Biol Chem"},{"key":"8054_CR8","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1161\/CIRCULATIONAHA.110.982777","volume":"123","author":"M Kawaguchi","year":"2011","unstructured":"Kawaguchi, M. et al. Inflammasome activation of cardiac fibroblasts is essential for myocardial ischemia\/reperfusion injury. Circulation \n                           123, 594\u2013604 (2011).","journal-title":"Circulation"},{"key":"8054_CR9","doi-asserted-by":"publisher","first-page":"19725","DOI":"10.1073\/pnas.1108586108","volume":"108","author":"E Mezzaroma","year":"2011","unstructured":"Mezzaroma, E. et al. The inflammasome promotes adverse cardiac remodeling following acute myocardial infarction in the mouse. Proc Natl Acad Sci USA \n                           108, 19725\u201319730 (2011).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"8054_CR10","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1681\/ASN.2010020143","volume":"21","author":"A Vilaysane","year":"2010","unstructured":"Vilaysane, A. et al. The NLRP3 inflammasome promotes renal inflammation and contributes to CKD. J Am Soc Nephrol \n                           21, 1732\u20131744 (2010).","journal-title":"J Am Soc Nephrol"},{"key":"8054_CR11","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S1097-2765(02)00599-3","volume":"10","author":"F Martinon","year":"2002","unstructured":"Martinon, F., Burns, K. & Tschopp, J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell \n                           10, 417\u2013426 (2002).","journal-title":"Mol Cell"},{"key":"8054_CR12","doi-asserted-by":"publisher","first-page":"21119","DOI":"10.1074\/jbc.C200179200","volume":"277","author":"SM Srinivasula","year":"2002","unstructured":"Srinivasula, S. M. et al. The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J Biol Chem \n                           277, 21119\u201321122 (2002).","journal-title":"J Biol Chem"},{"key":"8054_CR13","doi-asserted-by":"publisher","first-page":"10901","DOI":"10.1038\/srep10901","volume":"5","author":"T Komada","year":"2015","unstructured":"Komada, T. et al. Role of NLRP3 Inflammasomes for Rhabdomyolysis-induced Acute Kidney Injury. Sci Rep \n                           5, 10901 (2015).","journal-title":"Sci Rep"},{"key":"8054_CR14","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/ki.2014.271","volume":"87","author":"K Shahzad","year":"2015","unstructured":"Shahzad, K. et al. Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy. Kidney Int \n                           87, 74\u201384 (2015).","journal-title":"Kidney Int"},{"key":"8054_CR15","doi-asserted-by":"publisher","first-page":"25101","DOI":"10.1074\/jbc.M114.578260","volume":"289","author":"Y Zhuang","year":"2014","unstructured":"Zhuang, Y. et al. NLRP3 inflammasome mediates albumin-induced renal tubular injury through impaired mitochondrial function. J Biol Chem \n                           289, 25101\u201325111 (2014).","journal-title":"J Biol Chem"},{"key":"8054_CR16","doi-asserted-by":"publisher","first-page":"27159","DOI":"10.1074\/jbc.M114.567537","volume":"289","author":"JM Abais","year":"2014","unstructured":"Abais, J. M. et al. Nod-like receptor protein 3 (NLRP3) inflammasome activation and podocyte injury via thioredoxin-interacting protein (TXNIP) during hyperhomocysteinemia. J Biol Chem \n                           289, 27159\u201327168 (2014).","journal-title":"J Biol Chem"},{"key":"8054_CR17","doi-asserted-by":"publisher","first-page":"e3791","DOI":"10.1371\/journal.pone.0003791","volume":"3","author":"TE Sussan","year":"2008","unstructured":"Sussan, T. E. et al. Disruption of Nrf2, a key inducer of antioxidant defenses, attenuates ApoE-mediated atherosclerosis in mice. PLoS One \n                           3, e3791 (2008).","journal-title":"PLoS One"},{"key":"8054_CR18","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1161\/ATVBAHA.110.210906","volume":"31","author":"B Barajas","year":"2011","unstructured":"Barajas, B. et al. NF-E2-related factor 2 promotes atherosclerosis by effects on plasma lipoproteins and cholesterol transport that overshadow antioxidant protection. Arterioscler Thromb Vasc Biol \n                           31, 58\u201366 (2011).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"8054_CR19","doi-asserted-by":"publisher","first-page":"2040","DOI":"10.1002\/eji.201041316","volume":"41","author":"S Freigang","year":"2011","unstructured":"Freigang, S. et al. Nrf2 is essential for cholesterol crystal-induced inflammasome activation and exacerbation of atherosclerosis. Eur J Immunol \n                           41, 2040\u20132051 (2011).","journal-title":"Eur J Immunol"},{"key":"8054_CR20","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1038\/nature08938","volume":"464","author":"P Duewell","year":"2010","unstructured":"Duewell, P. et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature \n                           464, 1357\u20131361 (2010).","journal-title":"Nature"},{"key":"8054_CR21","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.1161\/CIRCULATIONAHA.107.746453","volume":"117","author":"N Yajima","year":"2008","unstructured":"Yajima, N. et al. Critical role of bone marrow apoptosis-associated speck-like protein, an inflammasome adaptor molecule, in neointimal formation after vascular injury in mice. Circulation \n                           117, 3079\u20133087 (2008).","journal-title":"Circulation"},{"key":"8054_CR22","doi-asserted-by":"publisher","first-page":"9292","DOI":"10.1074\/jbc.M109.093955","volume":"285","author":"J Pi","year":"2010","unstructured":"Pi, J. et al. Deficiency in the nuclear factor E2-related factor-2 transcription factor results in impaired adipogenesis and protects against diet-induced obesity. J Biol Chem \n                           285, 9292\u20139300 (2010).","journal-title":"J Biol Chem"},{"key":"8054_CR23","doi-asserted-by":"publisher","first-page":"2465","DOI":"10.2337\/db11-0112","volume":"60","author":"DV Chartoumpekis","year":"2011","unstructured":"Chartoumpekis, D. V. et al. Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice. Diabetes \n                           60, 2465\u20132473 (2011).","journal-title":"Diabetes"},{"key":"8054_CR24","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1006\/bbrc.1997.6943","volume":"236","author":"K Itoh","year":"1997","unstructured":"Itoh, K. et al. An Nrf2\/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun \n                           236, 313\u2013322 (1997).","journal-title":"Biochem Biophys Res Commun"},{"key":"8054_CR25","doi-asserted-by":"publisher","first-page":"3425","DOI":"10.1172\/JCI57582","volume":"121","author":"K Fujiu","year":"2011","unstructured":"Fujiu, K., Manabe, I. & Nagai, R. Renal collecting duct epithelial cells regulate inflammation in tubulointerstitial damage in mice. J Clin Invest \n                           121, 3425\u20133441 (2011).","journal-title":"J Clin Invest"},{"key":"8054_CR26","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1016\/j.ajpath.2014.01.014","volume":"184","author":"T Komada","year":"2014","unstructured":"Komada, T. et al. ASC in renal collecting duct epithelial cells contributes to inflammation and injury after unilateral ureteral obstruction. Am J Pathol \n                           184, 1287\u20131298 (2014).","journal-title":"Am J Pathol"},{"key":"8054_CR27","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1096\/fj.15-271734","volume":"29","author":"H Kadoya","year":"2015","unstructured":"Kadoya, H. et al. Excess aldosterone is a critical danger signal for inflammasome activation in the development of renal fibrosis in mice. FASEB J \n                           29, 3899\u20133910 (2015).","journal-title":"FASEB J"},{"key":"8054_CR28","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/ki.2012.475","volume":"83","author":"Y Nishi","year":"2013","unstructured":"Nishi, Y. et al. Selective estrogen receptor modulation attenuates proteinuria-induced renal tubular damage by modulating mitochondrial oxidative status. Kidney Int \n                           83, 662\u2013673 (2013).","journal-title":"Kidney Int"},{"key":"8054_CR29","doi-asserted-by":"publisher","first-page":"21884","DOI":"10.1038\/srep21884","volume":"6","author":"Z Su","year":"2016","unstructured":"Su, Z. et al. HMGB1 Facilitated Macrophage Reprogramming towards a Proinflammatory M1-like Phenotype in Experimental Autoimmune Myocarditis Development. Sci Rep \n                           6, 21884 (2016).","journal-title":"Sci Rep"},{"key":"8054_CR30","doi-asserted-by":"publisher","first-page":"F69","DOI":"10.1152\/ajprenal.00484.2014","volume":"308","author":"S Tian","year":"2015","unstructured":"Tian, S. et al. HMGB1 exacerbates renal tubulointerstitial fibrosis through facilitating M1 macrophage phenotype at the early stage of obstructive injury. Am J Physiol Renal Physiol \n                           308, F69\u201375 (2015).","journal-title":"Am J Physiol Renal Physiol"},{"key":"8054_CR31","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/nm.2053","volume":"15","author":"J Xu","year":"2009","unstructured":"Xu, J. et al. Extracellular histones are major mediators of death in sepsis. Nat Med \n                           15, 1318\u20131321 (2009).","journal-title":"Nat Med"},{"key":"8054_CR32","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1038\/ni.1960","volume":"11","author":"EA Miao","year":"2010","unstructured":"Miao, E. A. et al. Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria. Nat Immunol \n                           11, 1136\u20131142 (2010).","journal-title":"Nat Immunol"},{"key":"8054_CR33","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1681\/ASN.2011111077","volume":"23","author":"R Allam","year":"2012","unstructured":"Allam, R. et al. Histones from dying renal cells aggravate kidney injury via TLR2 and TLR4. J Am Soc Nephrol \n                           23, 1375\u20131388 (2012).","journal-title":"J Am Soc Nephrol"},{"key":"8054_CR34","doi-asserted-by":"publisher","first-page":"2579","DOI":"10.1161\/ATVBAHA.115.305789","volume":"35","author":"J Cai","year":"2015","unstructured":"Cai, J. et al. HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4. Arterioscler Thromb Vasc Biol \n                           35, 2579\u20132593 (2015).","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"8054_CR35","first-page":"1768","volume":"370","author":"GM Chertow","year":"2014","unstructured":"Chertow, G. M., de Zeeuw, D. & Committee, B. S. Bardoxolone methyl in type 2 diabetes and advanced chronic kidney disease. N Engl J Med \n                           370, 1768 (2014).","journal-title":"N Engl J Med"},{"key":"8054_CR36","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1038\/ki.2013.248","volume":"84","author":"LM Shelton","year":"2013","unstructured":"Shelton, L. M., Park, B. K. & Copple, I. M. Role of Nrf2 in protection against acute kidney injury. Kidney Int \n                           84, 1090\u20131095 (2013).","journal-title":"Kidney Int"},{"key":"8054_CR37","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1016\/j.freeradbiomed.2010.01.021","volume":"48","author":"DH Shin","year":"2010","unstructured":"Shin, D. H. et al. The NRF2-heme oxygenase-1 system modulates cyclosporin A-induced epithelial-mesenchymal transition and renal fibrosis. Free Radic Biol Med \n                           48, 1051\u20131063 (2010).","journal-title":"Free Radic Biol Med"},{"key":"8054_CR38","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1161\/01.RES.0000119171.44657.45","volume":"94","author":"T Ishii","year":"2004","unstructured":"Ishii, T. et al. Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages: activation by oxidatively modified LDL and 4-hydroxynonenal. Circ Res \n                           94, 609\u2013616 (2004).","journal-title":"Circ Res"},{"key":"8054_CR39","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1038\/ni.2639","volume":"14","author":"FJ Sheedy","year":"2013","unstructured":"Sheedy, F. J. et al. CD36 coordinates NLRP3 inflammasome activation by facilitating intracellular nucleation of soluble ligands into particulate ligands in sterile inflammation. Nat Immunol \n                           14, 812\u2013820 (2013).","journal-title":"Nat Immunol"},{"key":"8054_CR40","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1016\/j.kint.2015.12.043","volume":"89","author":"AC Souza","year":"2016","unstructured":"Souza, A. C. et al. Antagonism of scavenger receptor CD36 by 5A peptide prevents chronic kidney disease progression in mice independent of blood pressure regulation. Kidney Int \n                           89, 809\u2013822 (2016).","journal-title":"Kidney Int"},{"key":"8054_CR41","doi-asserted-by":"publisher","first-page":"4463","DOI":"10.1016\/j.febslet.2006.07.015","volume":"580","author":"H Hagiwara","year":"2006","unstructured":"Hagiwara, H. et al. Bone marrow transplantation improves outcome in a mouse model of congenital muscular dystrophy. FEBS Lett \n                           580, 4463\u20134468 (2006).","journal-title":"FEBS Lett"},{"key":"8054_CR42","doi-asserted-by":"publisher","first-page":"15514","DOI":"10.1073\/pnas.1414859111","volume":"111","author":"J Yu","year":"2014","unstructured":"Yu, J. et al. Inflammasome activation leads to Caspase-1-dependent mitochondrial damage and block of mitophagy. Proc Natl Acad Sci USA \n                           111, 15514\u201315519 (2014).","journal-title":"Proc Natl Acad Sci USA"},{"key":"8054_CR43","doi-asserted-by":"publisher","first-page":"F1402","DOI":"10.1152\/ajprenal.00459.2011","volume":"302","author":"H Nagasu","year":"2012","unstructured":"Nagasu, H. et al. Endothelial dysfunction promotes the transition from compensatory renal hypertrophy to kidney injury after unilateral nephrectomy in mice. Am J Physiol Renal Physiol \n                           302, F1402\u20131408 (2012).","journal-title":"Am J Physiol Renal Physiol"},{"key":"8054_CR44","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/labinvest.2010.175","volume":"91","author":"M Satoh","year":"2011","unstructured":"Satoh, M. et al. Mitochondrial damage-induced impairment of angiogenesis in the aging rat kidney. Lab Invest \n                           91, 190\u2013202 (2011).","journal-title":"Lab Invest"},{"key":"8054_CR45","doi-asserted-by":"publisher","first-page":"D67","DOI":"10.1093\/nar\/gkv1276","volume":"44","author":"K Clark","year":"2016","unstructured":"Clark, K., Karsch-Mizrachi, I., Lipman, D. J., Ostell, J. & Sayers, E. W. GenBank. Nucleic Acids Res \n                           44, D67\u201372 (2016).","journal-title":"Nucleic Acids Res"},{"key":"8054_CR46","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.jim.2010.01.004","volume":"354","author":"S Dhanasekaran","year":"2010","unstructured":"Dhanasekaran, S., Doherty, T. M., Kenneth, J. & Group, T. B. T. S. Comparison of different standards for real-time PCR-based absolute quantification. J Immunol Methods \n                           354, 34\u201339 (2010).","journal-title":"J Immunol Methods"},{"key":"8054_CR47","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1038\/hr.2011.184","volume":"35","author":"H Nagasu","year":"2012","unstructured":"Nagasu, H. et al. Azelnidipine attenuates glomerular damage in Dahl salt-sensitive rats by suppressing sympathetic nerve activity. Hypertens Res \n                           35, 348\u2013355 (2012).","journal-title":"Hypertens Res"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08054-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08054-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08054-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T08:55:16Z","timestamp":1671785716000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-08054-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,18]]},"references-count":47,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["8054"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-08054-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,18]]},"assertion":[{"value":"7 February 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 July 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8801"}}