{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T19:56:25Z","timestamp":1781812585290,"version":"3.54.5"},"reference-count":21,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2021,1,5]],"date-time":"2021-01-05T00:00:00Z","timestamp":1609804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Grant for Advance Research in Education","award":["LS2018773"],"award-info":[{"award-number":["LS2018773"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20am0101123"],"award-info":[{"award-number":["JP20am0101123"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["19H03130"],"award-info":[{"award-number":["19H03130"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:p>\n                    Macrophages appearing in lesions are polarized toward M1 (for inflammation) and M2 (for anti-inflammation\/fibrosis) types. We analyzed immunophenotypes of macrophages appearing in myocardial lesion in rats injected once with isoproterenol (10 mg\/kg body weight). Inflammation following myocardial necrosis on day 1 was seen with a peak on days 3 and 5, and thereafter, reparative fibrosis developed on days 7 to 28. CD68\n                    <jats:sup>+<\/jats:sup>\n                    M1 macrophages were seen in the early stages of injury and inflammatory on days 1 to 7, and thereafter, CD163\n                    <jats:sup>+<\/jats:sup>\n                    M2 macrophages increased in the late stages of fibrosis on days 7 to 28. There was the polarization of M1 and M2 macrophages. The kinetics of macrophages reacting to Iba-1 and Galectin-3 was similar to that of M1 macrophages, indicating that Iba1- and Gal-3-positive macrophages might have functions of M1 type. Double immunofluorescence revealed that CD204- and MHC class II-positive macrophages are polarized toward M1 and M2 types, respectively. CCR2 messenger RNA expression is transiently elevated on day 1. Since CCR2 is a marker of blood monocytes, M1 macrophages might be recruited from blood monocytes. Collectively, macrophages expressing heterogeneous immunophenotypes participate in myocardial fibrosis. These findings would be useful for understanding the pathogenesis of myocardial fibrosis and analyzing myocardial toxicity.\n                  <\/jats:p>","DOI":"10.1177\/0192623320982526","type":"journal-article","created":{"date-parts":[[2021,1,13]],"date-time":"2021-01-13T17:24:57Z","timestamp":1610558697000},"page":"1048-1061","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Appearance of Heterogeneous Macrophages During Development of Isoproterenol-Induced Rat Myocardial Fibrosis"],"prefix":"10.1177","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0814-6613","authenticated-orcid":false,"given":"Masaaki","family":"Koga","sequence":"first","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan"},{"name":"Nippon Shinyaku Co. Ltd., Minami-ku, Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0060-0893","authenticated-orcid":false,"given":"Mohammad Rabiul","family":"Karim","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan"},{"name":"Department of Anatomy and Histology, Faculty of Veterinary Science, Bangladesh Agricultural University, Mymensingh, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Kuramochi","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Izawa","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Kuwamura","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyoji","family":"Yamate","sequence":"additional","affiliation":[{"name":"Laboratory of Veterinary Pathology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Izumisano City, Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,1,5]]},"reference":[{"key":"bibr1-0192623320982526","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00238"},{"key":"bibr2-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.052126"},{"key":"bibr3-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200522675"},{"key":"bibr4-0192623320982526","doi-asserted-by":"publisher","DOI":"10.2741\/2692"},{"key":"bibr5-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2019.09.012"},{"key":"bibr6-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309194"},{"key":"bibr7-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2006.05.003"},{"key":"bibr8-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.306565"},{"key":"bibr9-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1007\/BF01008018"},{"key":"bibr10-0192623320982526","doi-asserted-by":"publisher","DOI":"10.2131\/jts.27.165"},{"key":"bibr11-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.18-0599"},{"issue":"4","key":"bibr12-0192623320982526","first-page":"497","volume":"29","author":"Wijesundera KK","year":"2014","journal-title":"Histol Histopathol"},{"key":"bibr13-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0059-x"},{"key":"bibr14-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1406508111"},{"key":"bibr15-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-199810000-00006"},{"key":"bibr16-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcpa.2005.01.011"},{"key":"bibr17-0192623320982526","unstructured":"Yamashiro S, Takeya M, Nishi T, et al. Tumor-derived monocyte chemoattractant protein-1 induces intratumoral infiltration of monocyte-derived macrophage subpopulation in transplanted rat tumors. Am J Pathol. 1994;145(4):856\u2013867."},{"key":"bibr18-0192623320982526","doi-asserted-by":"crossref","unstructured":"Ohsawa K, Imai Y, Kanazawa H, Sasaki Y, Kohsaka S. Involvement of Iba1 in membrane ruffling and phagocytosis of macrophages\/microglia. J Cell Sci. 2000;113(pt 17):3073\u20133084.","DOI":"10.1242\/jcs.113.17.3073"},{"key":"bibr19-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2001.5388"},{"key":"bibr20-0192623320982526","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06161"},{"key":"bibr21-0192623320982526","doi-asserted-by":"publisher","DOI":"10.14252\/foodsafetyfscj.2016012"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623320982526","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0192623320982526","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623320982526","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:41:47Z","timestamp":1777653707000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0192623320982526"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,5]]},"references-count":21,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1177\/0192623320982526"],"URL":"https:\/\/doi.org\/10.1177\/0192623320982526","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,5]]}}}