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Article: 7-Hydroxycoumarin protects against cisplatin-induced acute kidney injury by inhibiting necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation

Title7-Hydroxycoumarin protects against cisplatin-induced acute kidney injury by inhibiting necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation
Authors
Keywords7-hydroxycoumarin
AKI
Cisplatin
Necroptosis
Proliferation
Issue Date2020
PublisherElsevier GmbH - Urban und Fischer Verlag. The Journal's web site is located at http://www.elsevier.com/locate/phytomed
Citation
Phytomedicine, 2020, v. 69, p. article no. 153202 How to Cite?
AbstractBackground: 7-Hydroxycoumarin (7-HC), also known as umbelliferon, is commonly found in Chinese herbs (e.g. Eucommiae Cortex, Prunellae Spica, Radix Angelicae Biseratae). Previous laboratory studies have indicated that 7-HC has anti-inflammatory, anti-oxidative, and anti-tumor effects. Cisplatin is a widely used chemotherapeutic agent for cancer. Nephrotoxicity is one of the limiting side effects of cisplatin use. Purpose: This study aimed to evaluate the renoprotective effect of 7-HC in a cisplatin-induced acute kidney injury (AKI) mouse model. Methods: AKI was induced in male C57BL/6 mice (aged 6–8 weeks) by a single intraperitoneal injection of cisplatin at 20 mg/kg. The mice received 7-HC at 30, 60, and 90 mg/kg intraperitoneally before or after cisplatin administration. Renal function, necroptosis, and cell proliferation were measured. Mechanisms underlying the reno-protective effect of 7-HC were explored in renal tubular epithelial cells treated with or without cisplatin. Results: In-vivo experiments showed that 7-HC significantly improved the loss in kidney function induced by cisplatin, as indicated by lower levels of serum creatinine and blood urea nitrogen, in AKI mice. Consistent herewith, cisplatin-induced tubular damage was alleviated by 7-HC as shown by morphological (periodic acid–Schiff staining) and kidney injury marker (KIM-1) analyses. We found that 7-HC suppressed renal necroptosis via the RIPK1/RIPK3/MLKL pathway and accelerated renal repair as evidenced by the upregulation of cyclin D1 in cisplatin-induced nephropathy. In-vitro experiments showed that knockdown of Sox9 attenuated the suppressive effect of 7-HC on KIM-1 and reversed the stimulatory effect of 7-HC on cyclin D1 expression in cisplatin-treated HK-2 cells, indicating that 7-HC may protect against AKI via a Sox9-dependent mechanism. Conclusion: 7-HC inhibits cisplatin-induced AKI by suppressing RIPK1/RIPK3/MLKL-mediated necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation. 7-HC may serve as a preventive and therapeutic agent for AKI.
Persistent Identifierhttp://hdl.handle.net/10722/284905
ISSN
2019 Impact Factor: 4.268
2015 SCImago Journal Rankings: 1.013

 

DC FieldValueLanguage
dc.contributor.authorWU, WF-
dc.contributor.authorWang, JN-
dc.contributor.authorLi, Z-
dc.contributor.authorWei, B-
dc.contributor.authorJin, J-
dc.contributor.authorGao, L-
dc.contributor.authorLi, HD-
dc.contributor.authorLi, J-
dc.contributor.authorChen, HY-
dc.contributor.authorMeng, XM-
dc.date.accessioned2020-08-07T09:04:10Z-
dc.date.available2020-08-07T09:04:10Z-
dc.date.issued2020-
dc.identifier.citationPhytomedicine, 2020, v. 69, p. article no. 153202-
dc.identifier.issn0944-7113-
dc.identifier.urihttp://hdl.handle.net/10722/284905-
dc.description.abstractBackground: 7-Hydroxycoumarin (7-HC), also known as umbelliferon, is commonly found in Chinese herbs (e.g. Eucommiae Cortex, Prunellae Spica, Radix Angelicae Biseratae). Previous laboratory studies have indicated that 7-HC has anti-inflammatory, anti-oxidative, and anti-tumor effects. Cisplatin is a widely used chemotherapeutic agent for cancer. Nephrotoxicity is one of the limiting side effects of cisplatin use. Purpose: This study aimed to evaluate the renoprotective effect of 7-HC in a cisplatin-induced acute kidney injury (AKI) mouse model. Methods: AKI was induced in male C57BL/6 mice (aged 6–8 weeks) by a single intraperitoneal injection of cisplatin at 20 mg/kg. The mice received 7-HC at 30, 60, and 90 mg/kg intraperitoneally before or after cisplatin administration. Renal function, necroptosis, and cell proliferation were measured. Mechanisms underlying the reno-protective effect of 7-HC were explored in renal tubular epithelial cells treated with or without cisplatin. Results: In-vivo experiments showed that 7-HC significantly improved the loss in kidney function induced by cisplatin, as indicated by lower levels of serum creatinine and blood urea nitrogen, in AKI mice. Consistent herewith, cisplatin-induced tubular damage was alleviated by 7-HC as shown by morphological (periodic acid–Schiff staining) and kidney injury marker (KIM-1) analyses. We found that 7-HC suppressed renal necroptosis via the RIPK1/RIPK3/MLKL pathway and accelerated renal repair as evidenced by the upregulation of cyclin D1 in cisplatin-induced nephropathy. In-vitro experiments showed that knockdown of Sox9 attenuated the suppressive effect of 7-HC on KIM-1 and reversed the stimulatory effect of 7-HC on cyclin D1 expression in cisplatin-treated HK-2 cells, indicating that 7-HC may protect against AKI via a Sox9-dependent mechanism. Conclusion: 7-HC inhibits cisplatin-induced AKI by suppressing RIPK1/RIPK3/MLKL-mediated necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation. 7-HC may serve as a preventive and therapeutic agent for AKI.-
dc.languageeng-
dc.publisherElsevier GmbH - Urban und Fischer Verlag. The Journal's web site is located at http://www.elsevier.com/locate/phytomed-
dc.relation.ispartofPhytomedicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subject7-hydroxycoumarin-
dc.subjectAKI-
dc.subjectCisplatin-
dc.subjectNecroptosis-
dc.subjectProliferation-
dc.title7-Hydroxycoumarin protects against cisplatin-induced acute kidney injury by inhibiting necroptosis and promoting Sox9-mediated tubular epithelial cell proliferation-
dc.typeArticle-
dc.identifier.emailChen, HY: haiyong@hku.hk-
dc.identifier.authorityChen, HY=rp01923-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.phymed.2020.153202-
dc.identifier.pmid32169782-
dc.identifier.scopuseid_2-s2.0-85081037583-
dc.identifier.hkuros311889-
dc.identifier.volume69-
dc.identifier.spagearticle no. 153202-
dc.identifier.epagearticle no. 153202-
dc.publisher.placeGermany-

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