Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
Obesity/Type II diabetes alters macrophage polarization resulting in a fibrotic tendon healing response.
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DOI：
10.1371/journal.pone.0181127
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Loiselle AE
中科院分区：
文献类型：
--
作者：
Ackerman JE;Geary MB;Orner CA;Bawany F;Loiselle AE
与非糖尿病肌腱相比，2型糖尿病(T2 DM)严重损害肌腱的愈合反应，导致胶原组织和力学性能降低。尽管有这样的负担，但关于糖尿病肌腱愈合受损的机制仍然缺乏信息。小鼠接受高脂饮食(T2 DM)或低脂饮食(LEAN)，并接受屈肌腱切断和修复手术。通过力学测试、组织学和与胶原合成、基质重塑和巨噬细胞极化相关的基因表达的变化来评估愈合情况。肥胖/糖尿病肌腱愈合，疤痕形成增加，力学性能受损。与此一致的是，肥胖症/T2 DM肌腱中细胞外基质(ECM)成分的表达延长并过度表达。巨噬细胞在愈合过程中同时参与炎症和基质沉积过程。肥胖/T2 DM肌腱愈合，促炎症的M1巨噬细胞标志物表达增加，参与ECM沉积的M2巨噬细胞标志物表达增强且持续时间延长。在这里，我们证明肥胖/糖尿病小鼠的肌腱愈合时瘢痕形成增加，M2极化增加，确认过度的M2巨噬细胞活性和基质合成是T2 DM肌腱纤维化愈合表型的潜在机制，并因此成为改善T2 DM肌腱愈合的潜在靶点。
Type II Diabetes (T2DM) dramatically impairs the tendon healing response, resulting in decreased collagen organization and mechanics relative to non-diabetic tendons. Despite this burden, there remains a paucity of information regarding the mechanisms that govern impaired healing of diabetic tendons. Mice were placed on either a high fat diet (T2DM) or low fat diet (lean) and underwent flexor tendon transection and repair surgery. Healing was assessed via mechanical testing, histology and changes in gene expression associated with collagen synthesis, matrix remodeling, and macrophage polarization. Obese/diabetic tendons healed with increased scar formation and impaired mechanical properties. Consistent with this, prolonged and excess expression of extracellular matrix (ECM) components were observed in obese/T2DM tendons. Macrophages are involved in both inflammatory and matrix deposition processes during healing. Obese/T2DM tendons healed with increased expression of markers of pro-inflammatory M1 macrophages, and elevated and prolonged expression of M2 macrophages markers that are involved in ECM deposition. Here we demonstrate that tendons from obese/diabetic mice heal with increased scar formation and increased M2 polarization, identifying excess M2 macrophage activity and matrix synthesis as a potential mechanism of the fibrotic healing phenotype observed in T2DM tendons, and as such a potential target to improve tendon healing in T2DM.
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影响因子：
3.8
作者：
Connizzo, Brianne K.;Bhatt, Pankti R.;Liechty, Kenneth W.;Soslowsky, Louis J.
通讯作者：
Soslowsky, Louis J.
影响因子：
3.6
作者：
Ahmed, Aisha S.;Li, Jian;Ackermann, Paul W.
通讯作者：
Ackermann, Paul W.
影响因子：
1.9
作者：
Dong, Liang;Wang, Shu-Juan;Bi, Wen-Xiang
通讯作者：
Bi, Wen-Xiang
DOI：
10.1152/ajpendo.90617.2008
发表时间：
2008-12-01
影响因子：
5.1
作者：
Andrikopoulos, Sofianos;Blair, Amy R.;Proietto, Joseph
通讯作者：
Proietto, Joseph
影响因子：
3.3
作者：
Ahmed, Aisha S.;Schizas, Nikos;Ackermann, Paul W.
通讯作者：
Ackermann, Paul W.