Response by Li et al to Letter Regarding Article, "gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration".

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HomeCirculationVol. 143, No. 15Response by Li et al to Letter Regarding Article, “gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse by Li et al to Letter Regarding Article, “gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration” Yandong Li, Jie Feng and Yu Nie Yandong LiYandong Li State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for more papers by this author , Jie FengJie Feng State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for more papers by this author and Yu NieYu Nie https://orcid.org/0000-0002-8744-0046 State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Search for more papers by this author Originally published12 Apr 2021https://doi.org/10.1161/CIRCULATIONAHA.120.052610Circulation. 2021;143:e813–e814In Response:We were delighted that Chen et al noticed the significant effect of OSM (oncostatin M) presented in our article.1 OSM exerts different functions in heart and liver, which induces cardiomyocyte dedifferentiation2 and liver fibrosis,3 respectively. We revealed that OSM induced cardiomyocyte proliferation during heart regeneration, which is mediated by gp130 (glycoprotein 130) activation.1 Then, we proved that gp130 activation via adenovirus-associated virus serotype 9–gp130ACT delivery could be a potential approach for heart regeneration and cardiac repair (see Figure 7F to 7J1). It is important to note that the adenovirus-associated virus serotype 9–gp130ACT was cTnT (cardiac troponin T) promoter–guided and highly infected the heart instead of the liver.4Whether “the hepatic or nonhepatic fibrosis caused by the secretion of OSM in immature mice” is not in question, because gp130 is the downstream receptor of OSM and its activation with adenovirus-associated virus serotype 9–gp130ACT promotes cardiomyocyte proliferation and heart regeneration in adult mice (6–8 weeks old) (see Figure 7F to 7J1).Han et al has revealed that STAT3 (signal transducer and activator of transcription 3) pathway activation promotes cardiomyocyte proliferation and heart regeneration.5 Here, we found that both STAT3 and Yap (yes-associated protein) were activated in cardiomyocytes when gp130 was stimulated by OSM. In this study, we identified that gp130 promoted cardiomyocyte proliferation via stimulating the Src–Yap pathway. Meantime, we found that inhibition of STAT3 did not impair the effect of gp130–Src–Yap in cardiomyocyte proliferation and heart regeneration (see Figure XC in the Data Supplement1).Our results showed that macrophages that were recruited after cardiac injury secreted OSM and enhanced heart regeneration. Then, we conditionally deleted OSM in macrophages and found that neonatal heart regeneration was suspended, which could be rescued by OSM administration (see Figure 1J1), indicating that injury-recruited macrophages promoted neonatal heart regeneration by secreting OSM.Disclosures None.Footnoteshttps://www.ahajournals.org/journal/circ