Severe burn injury induces a myriad of deleterious effects to skeletal muscle, resulting in impaired function and delayed recovery. Following burn, catabolic signaling and myofiber atrophy are key fiber-intrinsic determinants of weakness; less well understood are alterations in the interstitial environment surrounding myofibers. Muscle quality, specifically alterations in the extracellular matrix (ECM), modulates force transmission and strength. We sought to determine the impact of severe thermal injury on adaptation to the muscle ECM and quantify muscle fibrotic burden. After a 30% total body surface area dorsal burn, spinotrapezius muscle was harvested from mice at 7 (7d, n = 5), 14 (14d, n = 4), and 21 days (21d, n = 4), and a sham control group was also examined (Sham, n = 4). Expression of transforming growth factor-β (TGFβ), myostatin, and downstream effectors and proteases involved in fibrosis and collagen remodeling were measured by immunoblotting, and immunohistochemical and biochemical analyses assessed fibrogenic cell abundance and collagen deposition. Myostatin signaling increased progressively through 21 days postburn alongside fibrogenic/adipogenic progenitor cell expansion, with abundance peaking at 14 days postburn. Postburn, elevated expression of tissue inhibitor of matrix metalloproteinase 1 supported collagen remodeling resulting in a net accumulation of muscle collagen content. Collagen accumulation peaked at 14 days postburn but remained elevated through 21 days postburn, demonstrating minimal resolution of burn-induced fibrosis. These findings highlight a progressive upregulation of fibrogenic processes following burn injury, eliciting a fibrotic muscle phenotype that hinders regenerative capacity and is not resolved with 21 days of recovery.

中文翻译：

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热损伤在骨骼肌中引发普遍的纤维化。

严重的烧伤会对骨骼肌产生无数有害影响，导致功能受损和恢复延迟。烧伤后，分解代谢信号和肌纤维萎缩是导致虚弱的关键纤维内在决定因素；不太清楚的是围绕肌纤维的间质环境的改变。肌肉质量，特别是细胞外基质 (ECM) 的改变，调节力的传递和力量。我们试图确定严重热损伤对肌肉 ECM 适应的影响并量化肌肉纤维化负担。背部烧伤 30% 全身表面积后，在第 7（7 天，n = 5）、14（14天，n = 4）和 21 天（21 天，n = 5）和 21 天（21 天，n= 4），并且还检查了一个假对照组（Sham，n= 4）。通过免疫印迹法测量转化生长因子-β (TGFβ)、肌生长抑制素、下游效应物和蛋白酶的表达，这些效应物和蛋白酶参与纤维化和胶原重塑，免疫组织化学和生化分析评估了纤维化细胞丰度和胶原沉积。肌肉生长抑制素信号在烧伤后 21 天随着纤维化/脂肪生成祖细胞的扩增而逐渐增加，丰度在烧伤后 14 天达到峰值。烧伤后，基质金属蛋白酶 1 组织抑制剂的表达升高支持胶原重塑，导致肌肉胶原含量的净积累。胶原蛋白积聚在烧伤后 14 天达到峰值，但在烧伤后 21 天保持升高，表明烧伤诱导的纤维化的最小分辨率。