Matrix-bound nanovesicle-associated IL-33 supports functional recovery after skeletal muscle injury by initiating a pro-regenerative macrophage phenotypic transition.
Matrix-bound nanovesicle-associated IL-33 supports functional recovery after skeletal muscle injury by initiating a pro-regenerative macrophage phenotypic transition.
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DOI：
10.1038/s41536-024-00346-2
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发表时间：
2024-01-27
影响因子：
7.2
通讯作者：
Badylak, S. F.
中科院分区：
文献类型：
--
作者：
Bartolacci, J. G.;Behun, M. N.;Warunek, J. P.;Li, T.;Sahu, A.;Dwyer, G. K.;Lucas, A.;Rong, J.;Ambrosio, F.;Turnquist, H. R.;Badylak, S. F.
骨骼肌损伤是平民和军人最常见的损伤之一，占肢体损伤的近60%。严重肢体损伤的护理标准一直侧重于保肢手术和利用组织移植物或矫形器结合康复，以避免截肢。尽管如此，许多患者具有持久的力量和功能缺陷，这永久地影响了他们的生活质量。临床前和临床研究表明，通过植入由细胞外基质（ECM）组成的生物支架，可以实现损伤后功能性骨骼肌组织的部分恢复。这些有利的结果至少部分是通过局部免疫调节介导的。然而，这种免疫调节作用的机制还知之甚少。本研究调查了免疫调节作用的潜在机制驱动因素;具体而言，所选ECM组分对炎症消退和修复的影响。结果表明，在损伤后14天，与年龄和性别匹配的野生型小鼠相比，il 33 −/−小鼠对骨骼肌损伤的宿主反应发生了深刻的改变，功能恢复下降。结果还表明，与未处理的il 33 −/−对应物相比，包含在基质结合纳米囊泡（MBV）中的IL-33通过经典和非经典途径调节局部巨噬细胞活化朝向促重塑表型来支持骨骼肌再生，以改善损伤的功能恢复。总之，这些数据表明MBV及其相关的IL-33货物代表了一种新的稳态信号传导机制，有助于骨骼肌修复。
Injuries to skeletal muscle are among the most common injuries in civilian and military populations, accounting for nearly 60% of extremity injuries. The standard of care for severe extremity injury has been focused upon limb salvage procedures and the utilization of tissue grafts or orthotics in conjunction with rehabilitation to avoid amputation. Nonetheless, many patients have persistent strength and functional deficits that permanently impact their quality of life. Preclinical and clinical studies have shown that partial restoration of functional skeletal muscle tissue following injury can be achieved by the implantation of a biologic scaffold composed of extracellular matrix (ECM). These favorable outcomes are mediated, at least in part, through local immunomodulation. The mechanisms underlying this immunomodulatory effect, however, are poorly understood. The present study investigates a potential mechanistic driver of the immunomodulatory effects; specifically, the effect of selected ECM components upon inflammation resolution and repair. Results show that the host response to skeletal muscle injury is profoundly altered and functional recovery decreased in il33−/− mice compared to age- and sex-matched wildtype counterparts by 14 days post-injury. Results also show that IL-33, contained within matrix-bound nanovesicles (MBV), supports skeletal muscle regeneration by regulating local macrophage activation toward a pro-remodeling phenotype via canonical and non-canonical pathways to improve functional recovery from injury compared to untreated il33−/− counterparts. Taken together, these data suggest that MBV and their associated IL-33 cargo represent a novel homeostatic signaling mechanism that contributes to skeletal muscle repair.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
7.4
作者：
Ambrosio, Fabrisia;Brown, Elke;Stolz, Donna;Ferrari, Ricardo;Goodpaster, Bret;Deasy, Bridget;Distefano, Giovanna;Roperti, Alexandra;Cheikhi, Amin;Garciafigueroa, Yesica;Barchowsky, Aaron
通讯作者：
Barchowsky, Aaron
影响因子：
7.8
作者：
Huleihel L;Dziki JL;Bartolacci JG;Rausch T;Scarritt ME;Cramer MC;Vorobyov T;LoPresti ST;Swineheart IT;White LJ;Brown BN;Badylak SF
通讯作者：
Badylak SF
影响因子：
4.1
作者：
Huleihel, Luai;Bartolacci, Joseph G.;Badylak, Stephen F.
通讯作者：
Badylak, Stephen F.
影响因子：
4.4
作者：
Milovanovic, Marija;Volarevic, Vladislav;Lukic, Miodrag L.
通讯作者：
Lukic, Miodrag L.