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HomeCirculationVol. 143, No. 15Letter by Chen et al 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/EPUBLetter by Chen et al Regarding Article, “gp130 Controls Cardiomyocyte Proliferation and Heart Regeneration” Hui Chen, Yun Tang and Zhanjun Yang Hui ChenHui Chen https://orcid.org/0000-0003-0582-903X Department of Geriatrics (H.C.) Search for more papers by this author , Yun TangYun Tang Department of Laboratory Medicine, Dalian Medical University, China (Y.T.). Search for more papers by this author and Zhanjun YangZhanjun Yang College of Chemistry & Chemical Engineering, Yangzhou University, China (Z.Y.). Search for more papers by this author Originally published12 Apr 2021https://doi.org/10.1161/CIRCULATIONAHA.120.052195Circulation. 2021;143:e811–e812To the Editor:We read with interest the paper by Li et al1 illustrating the importance of OSM (oncostatin M) receptor/gp130 (glycoprotein 130) in promoting the regeneration of mice cardiomyocytes through the Yap (yes-associated protein) pathway and a potential gene therapy to promote adult mice heart repair after myocardial infarction. However, OSM has different dedifferentiation and regeneration function in different tissues of diseases, such as inflammatory diseases and cancer.2 Adam et al also found that OSM, a growth factor, played an important role in promoting repair of distal finger defects in mice.3 Matsuda et al found that overexpression of OSM may lead to liver fibrosis by regulating hepatic stellate cells and macrophages balance in mice.4 The hepatic or nonhepatic fibrosis caused by the secretion of OSM in immature mice cannot be ignored in adenovirus-associated virus serotype 9–gp130ACT gene therapy.gp130 is an OSM receptor that is one of the important receptors to activate the STAT3 (signal transducer and activator of transcription 3) signal pathway.5 gp130 transmits information from extracellular to the nucleus to activate its target genes in the STAT3 pathway.5 STAT3 pathway is hyperactivated in different cancers, and the overexpression of OSM receptor/gp130 may result in cancer and chronic inflammation diseases.2If the distinctive mechanisms of the STAT3 pathway and the promotion of cardiomyocyte proliferation are not illustrative, the overexpression of gp130 causing tumorigenesis may hinder a possible gp130 gene therapy to improve heart regeneration after cardiac injury. The article by Li et al described that inhibition of the STAT3 pathway can inhibit the proliferation of cardiomyocytes, whereas inhibition of STAT3 signaling did not affect the Yap pathway,1 which does not mean there is no interaction between the 2 signal pathways. Moreover, Li et al did not elaborate on how the adenovirus-associated virus serotype 9–gp130ACT gene therapy promotes the recruitment of macrophages to repair heart cells, nor how this process occurs independently of the cancer-related STAT3 pathway. Therefore, in potential adenovirus-associated virus serotype 9–gp130ACT gene therapy, they cannot ignore the interaction between STAT3 and Yap pathways; otherwise, gp130 may activate tumor cell proliferation during clinical practice.In addition, Figure 1C1 may support our concerns that the OSM conditional knockout mice do not recover pumping function after apical resection operation. It was concluded that the reduction or knockout OSM had blocked neonatal heart regeneration, whereas there was no rescue experiment with OSM supplemented by Li et al. It is important that the rescue experiments be carried out to support their conclusion. Li et al showed that the reduction or knockout of OSM hindered the regeneration of neonatal heart cells; however, they did not support the conclusion further with supplemental OSM in remedial experiments.Sources of FundingThis study was supported by the National Natural Science Foundation of China (81573220) and the Foundation for Young Medical Scholars in Jiangsu Province (QNRC2016325, QNRC2016333).Disclosures None.Footnoteshttps://www.ahajournals.org/journal/circReferences1. Li Y, Feng J, Song S, Li H, Yang H, Zhou B, Li Y, Yue Z, Lian H, Liu L, et al. gp130 controls cardiomyocyte proliferation and heart regeneration.Circulation. 2020; 142:967–982. doi: 10.1161/CIRCULATIONAHA.119.044484LinkGoogle Scholar2. Jones SA, Jenkins BJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer.Nat Rev Immunol. 2018; 18:773–789. doi: 10.1038/s41577-018-0066-7CrossrefMedlineGoogle Scholar3. Johnston AP, Yuzwa SA, Carr MJ, Mahmud N, Storer MA, Krause MP, Jones K, Paul S, Kaplan DR, Miller FD. Dedifferentiated Schwann cell precursors secreting paracrine factors are required for regeneration of the mammalian digit tip.Cell Stem Cell. 2016; 19:433–448. doi: 10.1016/j.stem.2016.06.002CrossrefMedlineGoogle Scholar4. Matsuda M, Tsurusaki S, Miyata N, Saijou E, Okochi H, Miyajima A, Tanaka M. Oncostatin M causes liver fibrosis by regulating cooperation between hepatic stellate cells and macrophages in mice.Hepatology. 2018; 67:296–312. doi: 10.1002/hep.29421CrossrefMedlineGoogle Scholar5. Johnson DE, O’Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer.Nat Rev Clin Oncol. 2018; 15:234–248. doi: 10.1038/nrclinonc.2018.8CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails April 13, 2021Vol 143, Issue 15 Advertisement Article InformationMetrics © 2021 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.120.052195PMID: 33844582 Originally publishedApril 12, 2021 PDF download Advertisement SubjectsFunctional Magnetic Resonance Imaging (fMRI)