{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T15:33:22Z","timestamp":1781796802885,"version":"3.54.5"},"reference-count":83,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIDDK grants","award":["K99\/R00DK119413"],"award-info":[{"award-number":["K99\/R00DK119413"]}]},{"name":"NIDDK grants","award":["DK079337"],"award-info":[{"award-number":["DK079337"]}]},{"name":"NIDDK grants","award":["DK79337"],"award-info":[{"award-number":["DK79337"]}]},{"name":"NIDDK grants","award":["DK129239"],"award-info":[{"award-number":["DK129239"]}]},{"name":"P30 grant","award":["K99\/R00DK119413"],"award-info":[{"award-number":["K99\/R00DK119413"]}]},{"name":"P30 grant","award":["DK079337"],"award-info":[{"award-number":["DK079337"]}]},{"name":"P30 grant","award":["DK79337"],"award-info":[{"award-number":["DK79337"]}]},{"name":"P30 grant","award":["DK129239"],"award-info":[{"award-number":["DK129239"]}]},{"name":"UAB O\u2019Brien Center Grant","award":["K99\/R00DK119413"],"award-info":[{"award-number":["K99\/R00DK119413"]}]},{"name":"UAB O\u2019Brien Center Grant","award":["DK079337"],"award-info":[{"award-number":["DK079337"]}]},{"name":"UAB O\u2019Brien Center Grant","award":["DK79337"],"award-info":[{"award-number":["DK79337"]}]},{"name":"UAB O\u2019Brien Center Grant","award":["DK129239"],"award-info":[{"award-number":["DK129239"]}]},{"name":"R01","award":["K99\/R00DK119413"],"award-info":[{"award-number":["K99\/R00DK119413"]}]},{"name":"R01","award":["DK079337"],"award-info":[{"award-number":["DK079337"]}]},{"name":"R01","award":["DK79337"],"award-info":[{"award-number":["DK79337"]}]},{"name":"R01","award":["DK129239"],"award-info":[{"award-number":["DK129239"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Nephrotoxicity is the dose-limiting side-effect of the chemotherapeutic agent cisplatin (Cp). Recent evidence points to renal protective actions of G protein-coupled estrogen receptor 1 (GPER1). In addition, it has been shown that GPER1 signaling elicits protective actions against acute ischemic injuries that involve multiple organ systems; however, the involvement of GPER1 signaling in Cp-induced acute kidney injury (AKI) remains unclear. This study tested whether genetic deletion of GPER1 exacerbates Cp-induced AKI in male mice. We subjected male mice, homozygous (homo) and heterozygous (het) knockout for the GPER1 gene, and wild-type (WT) littermates to Cp or saline injections and assessed markers for renal injury on the third day after injections. We also determined serum levels of proinflammatory markers in saline and Cp-treated mice. Given the protective role of heme oxygenase-1 (HO-1) in Cp-mediated apoptosis, we also investigated genotypic differences in renal HO-1 abundance, cell death, and proliferation by Western blotting, the TUNEL assay, and Ki67 immunostaining, respectively. Cp increased serum creatinine, urea, and neutrophil gelatinase-associated lipocalin (NGAL) levels, the renal abundance of kidney injury molecule-1, and NGAL in all groups. Cp-induced AKI resulted in comparable histological evidence of injury in all genotypes. WT and homo mice showed greater renal HO-1 abundance in response to Cp. Renal HO-1 abundance was lower in Cp-treated homo, compared to Cp-treated WT mice. Of note, GPER1 deletion elicited a remarkable increase in renal apoptosis; however, no genotypic differences in cell proliferation were observed. Cp augmented kidney Ki67-positive counts, regardless of the genotype. Overall, our data do not support a role for GPER1 in mediating Cp-induced renal injury. GPER1 deletion promotes renal apoptosis and diminishes HO-1 induction in response to Cp, suggesting that GPER1 may play cytoprotective and anti-apoptotic actions in AKI. GPER1-induced regulation of HO-1 and apoptosis may offer novel therapeutic targets for the treatment of AKI.<\/jats:p>","DOI":"10.3390\/ijms23158284","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T21:11:05Z","timestamp":1658956265000},"page":"8284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Does G Protein-Coupled Estrogen Receptor 1 Contribute to Cisplatin-Induced Acute Kidney Injury in Male Mice?"],"prefix":"10.3390","volume":"23","author":[{"given":"Eman Y.","family":"Gohar","sequence":"first","affiliation":[{"name":"Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rawan N.","family":"Almutlaq","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlan","family":"Fan","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan S.","family":"Balkawade","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam K.","family":"Butt","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1522","DOI":"10.1016\/S0959-8049(98)00224-X","article-title":"Clinical development of platinum complexes in cancer therapy: An historical perspective and an update","volume":"34","author":"Lebwohl","year":"1998","journal-title":"Eur. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/S0272-6386(86)80111-1","article-title":"Cisplatin nephrotoxicity","volume":"8","author":"Safirstein","year":"1986","journal-title":"Am. J. Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/S0272-6386(86)80112-3","article-title":"Nephrotoxicity Induced by Cancer Chemotherapy with Special Emphasis on Cisplatin Toxicity","volume":"8","author":"Ries","year":"1986","journal-title":"Am. J. Kidney Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"967826","DOI":"10.1155\/2014\/967826","article-title":"Pathophysiology of cisplatin-induced acute kidney injury","volume":"2014","author":"Ozkok","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"332","DOI":"10.5935\/0101-2800.20130052","article-title":"Acute nephrotoxicity of cisplatin: Molecular mechanisms","volume":"35","author":"Peres","year":"2013","journal-title":"J. Bras. Nefrol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"McSweeney, K., Gadanec, L., Qaradakhi, T., Ali, B., Zulli, A., and Apostolopoulos, V. (2021). Mechanisms of Cisplatin-Induced Acute Kidney Injury: Pathological Mechanisms, Pharmacological Interventions, and Genetic Mitigations. Cancers, 13.","DOI":"10.3390\/cancers13071572"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"F740","DOI":"10.1152\/ajprenal.00049.2017","article-title":"Unique sex- and age-dependent effects in protective pathways in acute kidney injury","volume":"313","author":"Boddu","year":"2017","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Neugarten, J., Golestaneh, L., and Kolhe, N.V. (2018). Sex differences in acute kidney injury requiring dialysis. BMC Nephrol., 19.","DOI":"10.1186\/s12882-018-0937-y"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1007\/s11255-020-02761-y","article-title":"Renoprotective effects of estrogen on acute kidney injury: The role of SIRT1","volume":"53","author":"Mahani","year":"2021","journal-title":"Int. Urol. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Feng, J.-Y., Liu, K.-T., Abraham, E., Chen, C.-Y., Tsai, P.-Y., Chen, Y.-C., Lee, Y.-C., and Yang, K.-Y. (2014). Serum Estradiol Levels Predict Survival and Acute Kidney Injury in Patients with Septic Shock-A Prospective Study. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0097967"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"F612","DOI":"10.1152\/ajprenal.00045.2020","article-title":"G protein-coupled estrogen receptor 1 as a novel regulator of blood pressure","volume":"319","author":"Gohar","year":"2020","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.phrs.2013.02.008","article-title":"GPER: A novel target for non-genomic estrogen action in the cardiovascular system","volume":"71","author":"Han","year":"2013","journal-title":"Pharmacol. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.mce.2014.02.002","article-title":"Estrogen biology: New insights into GPER function and clinical opportunities","volume":"389","author":"Prossnitz","year":"2014","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s13293-019-0219-9","article-title":"Estrogen receptor profiles across tissues from male and female Rattus norvegicus","volume":"10","author":"Hutson","year":"2019","journal-title":"Biol. Sex Differ."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1016\/j.mce.2013.11.005","article-title":"Anatomical location and redistribution of G protein-coupled estrogen receptor-1 during the estrus cycle in mouse kidney and specific binding to estrogens but not aldosterone","volume":"382","author":"Cheng","year":"2013","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1161\/HYPERTENSIONAHA.111.175174","article-title":"Estrogen Receptor GPR30 Reduces Oxidative Stress and Proteinuria in the Salt-Sensitive Female mRen2.Lewis Rat","volume":"58","author":"Lindsey","year":"2011","journal-title":"Hypertension"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R297","DOI":"10.1152\/ajpregu.00267.2020","article-title":"Activation of G protein-coupled estrogen receptor 1 ameliorates proximal tubular injury and proteinuria in Dahl salt-sensitive female rats","volume":"320","author":"Gohar","year":"2021","journal-title":"Am. J. Physiol. Integr. Comp. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108666","DOI":"10.1016\/j.biopha.2019.108666","article-title":"G protein-coupled estrogen receptor activation improves contractile and diastolic functions in rat renal interlobular artery to protect against renal ischemia reperfusion injury","volume":"112","author":"Chang","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/biolre\/ioy043","article-title":"Estrogen in the male: A historical perspective","volume":"99","author":"Hess","year":"2018","journal-title":"Biol. Reprod."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1152\/physrev.00018.2016","article-title":"Estrogens in Male Physiology","volume":"97","author":"Cooke","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e13779","DOI":"10.1111\/and.13779","article-title":"Relationship between the G protein-coupled oestrogen receptor and spermatogenesis, and its correlation with male infertility","volume":"52","author":"Barut","year":"2020","journal-title":"Andrologia"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1530\/JME-16-0117","article-title":"GPER modulates tone and coronary vascular reactivity in male and female rats","volume":"59","author":"Debortoli","year":"2017","journal-title":"J. Mol. Endocrinol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.lfs.2018.09.036","article-title":"Sex difference in GPER expression does not change vascular relaxation or reactive oxygen species generation in rat mesenteric resistance arteries","volume":"211","author":"Peixoto","year":"2018","journal-title":"Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1161\/HYPERTENSIONAHA.111.184606","article-title":"Deletion of G Protein\u2013Coupled Estrogen Receptor Increases Endothelial Vasoconstriction","volume":"59","author":"Meyer","year":"2012","journal-title":"Hypertension"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"H1806","DOI":"10.1152\/ajpheart.00283.2009","article-title":"Activation of a novel estrogen receptor, GPER, is cardioprotective in male and female rats","volume":"297","author":"Deschamps","year":"2009","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"De Francesco, E.M., Angelone, T., Pasqua, T., Pupo, M., Cerra, M.C., and Maggiolini, M. (2013). GPER Mediates Cardiotropic Effects in Spontaneously Hypertensive Rat Hearts. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0069322"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ejps.2016.11.009","article-title":"Activation of GPER ameliorates experimental pulmonary hypertension in male rats","volume":"97","author":"Alencar","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Sharma, G., Hu, C., Staquicini, D.I., Brigman, J.L., Liu, M., Mauvais-Jarvis, F., Pasqualini, R., Arap, W., Arterburn, J.B., and Hathaway, H.J. (2020). Preclinical efficacy of the GPER-selective agonist G-1 in mouse models of obesity and diabetes. Sci. Transl. Med., 12.","DOI":"10.1126\/scitranslmed.aau5956"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1210\/en.2013-1357","article-title":"GPER Deficiency in Male Mice Results in Insulin Resistance, Dyslipidemia, and a Proinflammatory State","volume":"154","author":"Sharma","year":"2013","journal-title":"Endocrinology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"H16","DOI":"10.1152\/ajpheart.00588.2009","article-title":"A novel estrogen receptor GPER inhibits mitochondria permeability transition pore opening and protects the heart against ischemia-reperfusion injury","volume":"298","author":"Bopassa","year":"2010","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3892\/ijmm_00000452","article-title":"G-Protein coupled estrogen receptor 1 expression in rat and human heart: Protective role during ischaemic stress","volume":"26","author":"Randeva","year":"2010","journal-title":"Int. J. Mol. Med."},{"key":"ref_32","first-page":"4329","article-title":"Activation of G protein-coupled oestrogen receptor 1 at the onset of reperfusion protects the myocardium against ischemia\/reperfusion injury by reducing mitochondrial dysfunction and mitophagy","volume":"174","author":"Feng","year":"2017","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_33","first-page":"130060","article-title":"Chronic GPER activation prevents ischemia\/reperfusion injury in ovariectomized rats","volume":"1866","author":"Pardo","year":"2021","journal-title":"Biochim. Biophys. Acta (BBA)\u2014Gen. Subj."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.4103\/1673-5374.251571","article-title":"GPER agonist G1 suppresses neuronal apoptosis mediated by endoplasmic reticulum stress after cerebral ischemia\/reperfusion injury","volume":"14","author":"Si","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e00449","DOI":"10.1002\/brb3.449","article-title":"GPER expressed on microglia mediates the anti-inflammatory effect of estradiol in ischemic stroke","volume":"6","author":"Zhao","year":"2016","journal-title":"Brain Behav."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s13105-021-00846-5","article-title":"Estrogen alleviates hepatocyte necroptosis depending on GPER in hepatic ischemia reperfusion injury","volume":"78","author":"Li","year":"2021","journal-title":"J. Physiol. Biochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1042\/CS20180919","article-title":"Activation of G protein\u2013coupled estrogen receptor protects intestine from ischemia\/reperfusion injury in mice by protecting the crypt cell proliferation","volume":"133","author":"Chai","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_38","first-page":"173","article-title":"Apoptosis inducing factor mediates cisplatin-induced apoptosis of renal tubular epithelial cells","volume":"32","author":"Liu","year":"2010","journal-title":"Chin. J. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.3892\/ijmm.2014.1874","article-title":"Activation of G-protein-coupled receptor 40 attenuates the cisplatin-induced apoptosis of human renal proximal tubule epithelial cells","volume":"34","author":"Ma","year":"2014","journal-title":"Int. J. Mol. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"e015110","DOI":"10.1161\/JAHA.119.015110","article-title":"Evidence for G-Protein\u2013Coupled Estrogen Receptor as a Pronatriuretic Factor","volume":"9","author":"Gohar","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Hutchens, M.P., Kosaka, Y., Zhang, W., Fujiyoshi, T., Murphy, S., Alkayed, N., and Anderson, S. (2014). Estrogen-Mediated Renoprotection following Cardiac Arrest and Cardiopulmonary Resuscitation Is Robust to GPR30 Gene Deletion. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099910"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1681\/ASN.2019080767","article-title":"Inhibition of Estrogen Sulfotransferase (SULT1E1\/EST) Ameliorates Ischemic Acute Kidney Injury in Mice","volume":"31","author":"Zhou","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1097\/SHK.0000000000000586","article-title":"17\u03b2-Estradiol Accelerated Renal Tubule Regeneration in Male Rats After Ischemia\/Reperfusion-Induced Acute Kidney Injury","volume":"46","author":"Wu","year":"2016","journal-title":"Shock"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11010-018-3427-4","article-title":"Estradiol attenuates ischemia reperfusion-induced acute kidney injury through PPAR-gamma stimulated eNOS activation in rats","volume":"453","author":"Singh","year":"2019","journal-title":"Mol. Cell. Biochem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"17240","DOI":"10.1038\/s41598-020-73974-5","article-title":"A single dose of estrogen during hemorrhagic shock protects against Kidney Injury whereas estrogen restoration in ovariectomized mice is ineffective","volume":"10","author":"Cuny","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3109\/0886022X.2016.1155398","article-title":"The protective role of G protein-coupled estrogen receptor 1 (GPER-1) on methotrexate-induced nephrotoxicity in human renal epithelium cells","volume":"38","author":"Kurt","year":"2016","journal-title":"Ren. Fail."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"154","DOI":"10.2478\/enr-2019-0016","article-title":"Aldosterone rapidly activates p-PKC delta and GPR30 but suppresses p-PKC epsilon protein levels in rat kidney","volume":"53","author":"Chaipipat","year":"2019","journal-title":"Endocr. Regul."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1146\/annurev.pharmtox.010909.105600","article-title":"Mechanisms of Cell Protection by Heme Oxygenase-1","volume":"50","author":"Gozzelino","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1089\/ars.2016.6659","article-title":"Heme Oxygenase-1 in Kidney Health and Disease","volume":"25","author":"Lever","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1146\/annurev.pharmtox.37.1.517","article-title":"The Heme Oxygenase System: A Regulator of Second Messenger Gases","volume":"37","author":"Maines","year":"1997","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3109\/10715769009148577","article-title":"Induction of Haem Oxygenase as a Defence against Oxidative Stress","volume":"9","author":"Stocker","year":"1990","journal-title":"Free. Radic. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1097\/00003246-200003000-00033","article-title":"Protective effect of heme oxygenase induction in ischemic acute renal failure","volume":"28","author":"Shimizu","year":"2000","journal-title":"Crit. Care Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1097\/01.ASN.0000050760.87113.25","article-title":"Gene transfer-induced local heme oxygenase-1 overexpression protects rat kidney transplants from ischemia\/reperfusion injury","volume":"14","author":"Katori","year":"2003","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1681\/ASN.2010030238","article-title":"Heme Oxygenase-1 Inhibits Renal Tubular Macroautophagy in Acute Kidney Injury","volume":"21","author":"Bolisetty","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"F726","DOI":"10.1152\/ajprenal.2000.278.5.F726","article-title":"Heme oxygenase-1 gene ablation or expression modulates cisplatin-induced renal tubular apoptosis","volume":"278","author":"Shiraishi","year":"2000","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.2353\/ajpath.2007.061093","article-title":"Renal hemodynamic, inflammatory, and apoptotic responses to lipopolysaccharide in HO-1\u2212\/\u2212 mice","volume":"170","author":"Tracz","year":"2007","journal-title":"Am. J. Pathol."},{"key":"ref_57","first-page":"429713","article-title":"Endogenous Estrogen-Mediated Heme Oxygenase Regulation in Experimental Menopause","volume":"2015","author":"Csonka","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2005.02.033","article-title":"Oxidative stress induces vascular heme oxygenase-1 expression in ovariectomized rats","volume":"39","author":"Lee","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_59","first-page":"234","article-title":"Expression of heme oxygenase-1 in rat prostate and effects of androgen and estrogen on it","volume":"34","author":"Tian","year":"2003","journal-title":"Sichuan Da Xue Xue Bao. Yi Xue Ban = J. Sichuan Univ. Med Sci. Ed."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1161\/HYPERTENSIONAHA.110.153262","article-title":"Estradiol stimulates capillary formation by human endothelial progenitor cells: Role of estrogen receptor-\u03b1\/\u03b2, heme oxygenase 1, and tyrosine kinase","volume":"56","author":"Baruscotti","year":"2010","journal-title":"Hypertension"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1002\/jcp.29971","article-title":"Estrogen enhances browning in adipose tissue by M2 macrophage polarization via heme oxygenase-1","volume":"236","author":"Sul","year":"2020","journal-title":"J. Cell. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00210-018-1462-z","article-title":"Endothelin-1-induced hypertrophic alterations and heme oxygenase-1 expression in cardiomyoblasts are counteracted by beta estradiol: In vitro and in vivo studies","volume":"391","author":"Barta","year":"2018","journal-title":"Naunyn-Schmiedebergs Arch. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.jss.2012.10.926","article-title":"Role of Akt\/HO-1 pathway in estrogen-mediated attenuation of trauma-hemorrhage-induced lung injury","volume":"182","author":"Hsu","year":"2013","journal-title":"J. Surg. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"387","DOI":"10.23876\/j.krcp.20.091","article-title":"New insights into the role of heme oxygenase-1 in acute kidney injury","volume":"39","author":"Nath","year":"2020","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.trsl.2018.04.005","article-title":"G protein-coupled estrogen receptor (GPER) deficiency induces cardiac remodeling through oxidative stress","volume":"199","author":"Wang","year":"2018","journal-title":"Transl. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.1002\/jcp.25585","article-title":"Protective Role of GPER Agonist G-1 on Cardiotoxicity Induced by Doxorubicin","volume":"232","author":"Rocca","year":"2017","journal-title":"J. Cell. Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2292","DOI":"10.2337\/db09-0257","article-title":"Importance of Extranuclear Estrogen Receptor-\u03b1 and Membrane G Protein\u2013Coupled Estrogen Receptor in Pancreatic Islet Survival","volume":"58","author":"Liu","year":"2009","journal-title":"Diabetes"},{"key":"ref_68","first-page":"791","article-title":"Progesterone and estrogen prevent cisplatin-induced apoptosis of lung cancer cells","volume":"33","author":"Grott","year":"2013","journal-title":"Anticancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3625","DOI":"10.1111\/jcmm.15055","article-title":"Cisplatin resistance in gastric cancer cells is involved with GPR30-mediated epithelial-mesenchymal transition","volume":"24","author":"Wang","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.3389\/fonc.2019.01079","article-title":"Chronic BDE-47 Exposure Aggravates Malignant Phenotypes and Chemoresistance by Activating ERK Through ERalpha and GPR30 in Endometrial Carcinoma","volume":"9","author":"Zhang","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1681\/ASN.2018101025","article-title":"Rapid Aldosterone-Mediated Signaling in the DCT Increases Activity of the Thiazide-Sensitive NaCl Cotransporter","volume":"30","author":"Cheng","year":"2019","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"C532","DOI":"10.1152\/ajpcell.00203.2012","article-title":"Aldosterone mediates its rapid effects in vascular endothelial cells through GPER activation","volume":"304","author":"Gros","year":"2013","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fphar.2015.00034","article-title":"Diabetes impairs the vascular effects of aldosterone mediated by G protein-coupled estrogen receptor activation","volume":"6","author":"Ferreira","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"94","DOI":"10.18632\/oncotarget.6475","article-title":"GPER is involved in the stimulatory effects of aldosterone in breast cancer cells and breast tumor-derived endothelial cells","volume":"7","author":"Rigiracciolo","year":"2015","journal-title":"Oncotarget"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"6316","DOI":"10.1210\/jc.2019-00043","article-title":"Aldosterone Stimulates Its Biosynthesis Via a Novel GPER-Mediated Mechanism","volume":"104","author":"Caroccia","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"108486","DOI":"10.1016\/j.steroids.2019.108486","article-title":"Role of estrogen receptors in modulating aldosterone biosynthesis and blood pressure","volume":"152","author":"Rossi","year":"2019","journal-title":"Steroids"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e8046","DOI":"10.7717\/peerj.8046","article-title":"Oxidative stress as a potential target in acute kidney injury","volume":"7","author":"Tomsa","year":"2019","journal-title":"PeerJ"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5515","DOI":"10.21873\/anticanres.13744","article-title":"Protective Role of Fucoidan on Cisplatin-mediated ER Stress in Renal Proximal Tubule Epithelial Cells","volume":"39","author":"Kim","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Mapuskar, K.A., Steinbach, E.J., Zaher, A., Riley, D.P., Beardsley, R.A., Keene, J.L., Holmlund, J.T., Anderson, C.M., Zepeda-Orozco, D., and Buatti, J.M. (2021). Mitochondrial Superoxide Dismutase in Cisplatin-Induced Kidney Injury. Antioxidants, 10.","DOI":"10.3390\/antiox10091329"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1080\/0886022X.2018.1456938","article-title":"Cisplatin-induced oxidative stress stimulates renal Fas ligand shedding","volume":"40","author":"Soni","year":"2018","journal-title":"Ren. Fail."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.3892\/mmr.2015.3674","article-title":"Activation of novel estrogen receptor GPER results in inhibition of cardiocyte apoptosis and cardioprotection","volume":"12","author":"Li","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1159\/000478732","article-title":"GPER Mediates Functional Endothelial Aging in Renal Arteries","volume":"100","author":"Meyer","year":"2017","journal-title":"Pharmacology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"111429","DOI":"10.1016\/j.ecoenv.2020.111429","article-title":"Bisphenol A induces apoptosis through GPER-dependent activation of the ROS\/Ca2+-ASK1-JNK pathway in human granulosa cell line KGN","volume":"208","author":"Huang","year":"2021","journal-title":"Ecotoxicol. Environ. Saf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8284\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:57:39Z","timestamp":1760140659000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/15\/8284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":83,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23158284"],"URL":"https:\/\/doi.org\/10.3390\/ijms23158284","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,27]]}}}