{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:12:08Z","timestamp":1783980728691,"version":"3.55.0"},"reference-count":43,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Lymphatic Research and Biology"],"published-print":{"date-parts":[[2022,12,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Secondary lymphedema (LE) occurs due to the disruption of lymphatic circulation. Lymphatic fluid accumulation in subcutaneous tissues induces adipocyte proliferation. Obesity is an important risk factor for the occurrence and deterioration of LE. Although the relationship between LE and subcutaneous adipose tissue increase has been reported clinically, their pathophysiological relationship remains unknown. Thus, we aimed to verify whether subcutaneous adipose tissue increase is involved in the pathophysiology of secondary LE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>\n                      The hindlimb model of secondary LE was created using male Sprague\u2013Dawley rats (control and LE groups;\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20095 each). Skin samples were obtained on postoperative day 168. Histological examination and quantitative real-time polymerase chain reaction analysis of inflammatory adipokines,\n                      <jats:italic toggle=\"yes\">tumor necrosis factor-alpha (Tnf-\u03b1)<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">C-C chemokine ligand 2 (Ccl2)<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">interleukin-6<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Il-6<\/jats:italic>\n                      ) were performed. Limb volume and subcutaneous adipose tissues significantly increased in the LE group compared with those in the control. Macrophages aggregated in the augmented adipose tissues, around the adipocytes, and formed crown-like structures (CLSs). The number of CLSs significantly increased in the LE group. These macrophages expressed transforming growth factor-beta 1 (TGF-\u03b21). Inflammatory adipokine secretion was not observed. Although\n                      <jats:italic toggle=\"yes\">Il-6<\/jats:italic>\n                      expression increased in the LE group, IL-6 was expressed in subcutaneous myofibroblasts but not in subcutaneous adipocytes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>As TGF-\u03b21 derived from subcutaneous myofibroblasts is involved in skin fibrosis during LE, TGF-\u03b21 derived from adipose tissues may also play a similar role. Drug treatment for subcutaneous adipose tissue reduction may improve the skin condition in secondary LE and may be a new therapeutic strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/lrb.2021.0054","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T11:16:44Z","timestamp":1649416604000},"page":"593-599","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2601-0226","authenticated-orcid":false,"given":"Masaki","family":"Sano","sequence":"first","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Hirakawa","sequence":"additional","affiliation":[{"name":"Preeminent Medical Photonics Education and Research Center Institute for NanoSuit Research, Departments of Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Anatomy and Neuroscience and Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Inuzuka","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuto","family":"Katahashi","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takafumi","family":"Kayama","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Tsuyuki","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Endo","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ena","family":"Naruse","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurina","family":"Yokoyama","sequence":"additional","affiliation":[{"name":"Rehabilitation, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohji","family":"Sato","sequence":"additional","affiliation":[{"name":"Anatomy and Neuroscience and Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"Rehabilitation, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroya","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Unno","sequence":"additional","affiliation":[{"name":"Division of Vascular Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."},{"name":"Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2022,12,15]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(00)00727-0"},{"key":"e_1_3_4_3_2","volume-title":"F\u00f6ldi's Textbook of Lymphology: For Physicians and Lymphedema Therapists, 3rd Rev Ed","author":"F\u00f6ldi MFE","year":"2012","unstructured":"F\u00f6ldi MFE. F\u00f6ldi's Textbook of Lymphology: For Physicians and Lymphedema Therapists, 3rd Rev Ed. Munchen: Urban & Fischer; 2012."},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21253"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1089\/lrb.2018.0089"},{"key":"e_1_3_4_6_2","first-page":"193","article-title":"Quality-of-life and body image impairments in patients with lymphedema","volume":"39","author":"Jager G","year":"2006","unstructured":"Jager G, , Doller W, , Roth R. Quality-of-life and body image impairments in patients with lymphedema. Lymphology, 2006; 39:193\u2013200.","journal-title":"Lymphology"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0072-5"},{"key":"e_1_3_4_8_2","first-page":"170","article-title":"The diagnosis and treatment of peripheral lymphedema: 2016 consensus document of the International Society of Lymphology","volume":"49","author":"Executive Committee","year":"2016","unstructured":"Executive Committee. The diagnosis and treatment of peripheral lymphedema: 2016 consensus document of the International Society of Lymphology. Lymphology, 2016; 49:170\u2013184.","journal-title":"Lymphology"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.breast.2017.09.006"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22638"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/GOX.0000000000001912"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0b013e3182450b47"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(98)00200-7"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.85096"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00137"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500294-JLR200"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.5551\/jat.3939"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2013.02.003"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5982"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S73223"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.7150\/jca.16884"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14457"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.avsg.2017.01.023"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0741"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0303-6987.2003.00166.x"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0250169"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.73"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1005-1023"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1642"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.9.5039"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.2337\/db10-0864"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.645234"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M011338"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M800019-JLR200"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)39428-1"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200319246"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1651"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1155\/2010\/513948"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01019.2013"},{"key":"e_1_3_4_40_2","first-page":"2123","article-title":"TGF-\u03b2-induced interleukin-6 participates in transdifferentiation of human Tenon's fibroblasts to myofibroblasts","volume":"15","author":"Seong GJ","year":"2009","unstructured":"Seong GJ, , Hong S, , Jung SA, et al. TGF-\u03b2-induced interleukin-6 participates in transdifferentiation of human Tenon's fibroblasts to myofibroblasts. Mol Vis, 2009; 15:2123\u20132128.","journal-title":"Mol Vis"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1097\/00061198-200406000-00005"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1201684"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1991.70.5.2164"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.21.6.0415"}],"container-title":["Lymphatic Research and Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/lrb.2021.0054","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/lrb.2021.0054","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/lrb.2021.0054","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:14:07Z","timestamp":1777666447000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/lrb.2021.0054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,1]]},"references-count":43,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2022,12,1]]}},"alternative-id":["10.1089\/lrb.2021.0054"],"URL":"https:\/\/doi.org\/10.1089\/lrb.2021.0054","relation":{},"ISSN":["1539-6851","1557-8585"],"issn-type":[{"value":"1539-6851","type":"print"},{"value":"1557-8585","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,1]]}}}