HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in skeletal muscles.
HMGB2 is a novel adipogenic factor that regulates ectopic fat infiltration in skeletal muscles.
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DOI：
10.1038/s41598-018-28023-7
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发表时间：
2018-06-25
影响因子：
4.6
通讯作者：
Chosa E
中科院分区：
文献类型：
--
作者：
Lee D;Taniguchi N;Sato K;Choijookhuu N;Hishikawa Y;Kataoka H;Morinaga H;Lotz M;Chosa E
虽然已经开发了各种手术方法用于慢性肩袖撕裂修复，但由于严重脂肪浸润，再撕裂率仍然很高。然而，对这一过程的分子调控知之甚少。肌间隙的间充质干细胞是骨骼肌异位脂肪细胞的来源。我们以前已经表明，高迁移率族蛋白2（HMGB 2），这是一个核蛋白通常与间充质分化，参与早期关节软骨退变。在这项研究中，我们解决了HMGB 2在骨髓间充质干细胞脂肪形成和脂肪浸润到骨骼肌中的作用。HMGB 2在未分化的MSCs中高度表达，并与血小板衍生生长因子受体α（PDGFRA）共定位，后者是一种MSCs特异性标志物，而在脂肪细胞分化过程中，其表达降低。在HMGB 2缺乏的情况下，脂肪形成相关分子的表达减少，并且MSCs的脂肪形成分化受到实质性损害。此外，HMGB 2+细胞产生的大鼠冈上肌肌腹后，肩袖横断，这些细胞中的一些表达PDGFRA在肌内空间。因此，我们的研究结果表明，HMGB 2的表达增强诱导骨髓间充质干细胞的脂肪形成和脂肪浸润到骨骼肌通过HMGB 2-PDGFRA级联。
Although various surgical procedures have been developed for chronic rotator cuff tear repair, the re-tear rate remains high with severe fat infiltration. However, little is known about the molecular regulation of this process. Mesenchymal stem cells (MSCs) in the intra-muscular space are origin of ectopic fat cells in skeletal muscle. We have previously shown that high-mobility group box 2 (HMGB2), which is a nuclear protein commonly associated with mesenchymal differentiation, is involved in the early articular cartilage degeneration. In this study, we addressed the role of HMGB2 in adipogenesis of MSCs and fat infiltration into skeletal muscles. HMGB2 was highly expressed in undifferentiated MSCs and co-localized with platelet-derived growth factor receptor α (PDGFRA) known as an MSC-specific marker, while their expressions were decreased during adipocytic differentiation. Under the deficiency of HMGB2, the expressions of adipogenesis-related molecules were reduced, and adipogenic differentiation is substantially impaired in MSCs. Moreover, HMGB2+ cells were generated in the muscle belly of rat supraspinatus muscles after rotator cuff transection, and some of these cells expressed PDGFRA in intra-muscular spaces. Thus, our findings suggest that the enhance expression of HMGB2 induces the adipogenesis of MSCs and the fat infiltration into skeletal muscles through the cascade of HMGB2-PDGFRA.
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小鼠骨髓中多能间充质干细胞的前瞻性鉴定、分离和系统移植。
DOI：
10.1084/jem.20091046
发表时间：
2009-10-26
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Morikawa S;Mabuchi Y;Kubota Y;Nagai Y;Niibe K;Hiratsu E;Suzuki S;Miyauchi-Hara C;Nagoshi N;Sunabori T;Shimmura S;Miyawaki A;Nakagawa T;Suda T;Okano H;Matsuzaki Y
通讯作者：
Matsuzaki Y
DOI：
10.1083/jcb.201608026
发表时间：
2016-11-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Aird KM;Iwasaki O;Kossenkov AV;Tanizawa H;Fatkhutdinov N;Bitler BG;Le L;Alicea G;Yang TL;Johnson FB;Noma KI;Zhang R
通讯作者：
Zhang R
影响因子：
10.9
作者：
Christodoulides, Constantinos;Lagathu, Claire;Sethi, Jaswinder K.;Vidal-Puig, Antonio
通讯作者：
Vidal-Puig, Antonio
影响因子：
20.3
作者：
Laurent, Benoit;Randrianarison-Huetz, Voahangy;Dumenil, Dominique
通讯作者：
Dumenil, Dominique
影响因子：
10.5
作者：
Rosen, ED;Hsu, CH;Spiegelman, BM
通讯作者：
Spiegelman, BM