Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema
Role of Subcutaneous Adipose Tissues in the Pathophysiology of Secondary Lymphedema
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皮下脂肪组织在继发性淋巴水肿病理生理学中的作用
DOI：
10.1089/lrb.2021.0054
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发表时间：
2022
影响因子：
1.4
通讯作者：
Unno Naoki
中科院分区：
文献类型：
--
作者：
Sano Masaki;Hirakawa Satoshi;Sasaki Takeshi;Inuzuka Kazunori;Katahashi Kazuto;Kayama Takafumi;Yamanaka Yuta;Tsuyuki Hajime;Endo Yusuke;Naruse Ena;Yokoyama Yurina;Sato Kohji;Yamauchi Katsuya;Takeuchi Hiroya;Unno Naoki
背景：继发性水肿（LE）是由于淋巴循环中断而发生的。皮下组织中的淋巴液积聚诱导脂肪细胞增殖。肥胖是LE发生和恶化的重要危险因素。虽然LE和皮下脂肪组织增加之间的关系已在临床上报道，但其病理生理关系仍不清楚。因此，我们的目的是验证皮下脂肪组织的增加是否参与继发性LE.Methods和结果的病理生理学：后肢模型的继发性LE使用雄性Sprague-Dawley大鼠（对照组和LE组，n= 5）。在术后第168天采集皮肤样本。组织学检查和实时荧光定量聚合酶链反应分析炎性脂肪因子、肿瘤坏死因子-α（TNF-α）、C-C趋化因子配体2（Ccl 2）和白细胞介素-6（IL-6）。与对照组相比，LE组的肢体体积和皮下脂肪组织显著增加。巨噬细胞聚集在增生的脂肪组织中，围绕脂肪细胞，形成冠状结构（CLS）。LE组的CLS数量显著增加。这些巨噬细胞表达转化生长因子-β 1（TGF-β1）。未观察到炎性脂肪因子分泌。结论：LE时皮下肌成纤维细胞来源的TGF-β1参与皮肤纤维化，脂肪组织来源的TGF-β 1可能也参与皮肤纤维化。减少皮下脂肪组织的药物治疗可能改善继发性LE的皮肤状况，并可能成为一种新的治疗策略。
Background: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.Methods and Results:The hindlimb model of secondary LE was created using male Sprague–Dawley rats (control and LE groups;n= 5 each). Skin samples were obtained on postoperative day 168. Histological examination and quantitative real-time polymerase chain reaction analysis of inflammatory adipokines,tumor necrosis factor-alpha (Tnf-α),C-C chemokine ligand 2 (Ccl2), andinterleukin-6(Il-6) 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-β1). Inflammatory adipokine secretion was not observed. AlthoughIl-6expression increased in the LE group, IL-6 was expressed in subcutaneous myofibroblasts but not in subcutaneous adipocytes.Conclusion:As TGF-β1 derived from subcutaneous myofibroblasts is involved in skin fibrosis during LE, TGF-β1 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.