Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury
Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal Muscle Injury
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骨膜蛋白促进成纤维细胞迁移并抑制骨骼肌损伤后的肌肉修复
DOI：
10.2106/jbjs.17.01230
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发表时间：
2018-08-15
影响因子：
5.3
通讯作者：
Okada, Seiji
中科院分区：
文献类型：
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作者：
Hara, Masamitsu;Yokota, Kazuya;Okada, Seiji
背景：骨骼肌损伤（SMI）由于肌肉恢复不充分，可导致肢体残疾。SMI后肌肉纤维化的发展已被广泛认为是这种无法恢复的主要原因。骨膜蛋白（Postn）加剧各种器官中的组织纤维化。我们调查是否Postn参与SMI.Methods后的病理生理学：部分撕裂伤腓肠肌在野生型（WT）和Postn基因敲除（Postn（-/-））小鼠。我们检测了SMI前后Postn基因的表达。通过组织学分析评价骨骼肌的再生和纤维化，并通过生理测试测量肌肉力量的恢复。免疫组化法检测损伤肌肉中浸润成纤维细胞的数量和增殖能力。使用跨孔迁移测定来评估成纤维细胞的迁移能力。对照免疫球蛋白G（IgG）或Postn中和抗体（Postn-nAb）在损伤后7天和14天（dpi）注射到损伤的肌肉中。我们评估了Postn-nAb对SMI后肌肉修复的影响。结果：SMI后Postn的表达显著上调。与WT小鼠相比，Postn（-/-）小鼠具有改善的肌肉恢复和减弱的纤维化以及显著减少的浸润成纤维细胞数量。WT和Postn（-/-）小鼠中这些成纤维细胞的增殖潜力在14 dpi时相当;然而，在存在Postn的情况下，成纤维细胞的迁移能力显著增强（平均值，258%; 95%置信区间，183%至334%）。此外，Postn-nAb的管理抑制成纤维细胞浸润，促进肌肉修复后SMI.Conclusions：Postn加剧纤维化瘢痕形成，通过促进成纤维细胞迁移到受伤的肌肉后SMI。Postn-nAb治疗可有效减轻纤维化并改善SMI后的肌肉恢复。
Background: Skeletal muscle injury (SMI) can cause physical disability due to insufficient recovery of the muscle. The development of muscle fibrosis after SMI has been widely regarded as a principal cause of this failure to recover. Periostin (Postn) exacerbates tissue fibrosis in various organs. We investigated whether Postn is involved in the pathophysiology after SMI.Methods: Partial laceration injuries of the gastrocnemius were created in wild-type (WT) and Postn knockout (Postn(-/-)) mice. We examined the expression of the Postn gene before and after SMI. Regeneration and fibrosis of skeletal muscle were evaluated by histological analyses, and recovery of muscle strength was measured by physiological testing. Immunohistochemistry was used to examine the number and proliferative potential of infiltrating fibroblasts in injured muscle. A trans-well migration assay was used to assess the migration capability of fibroblasts. Control immunoglobulin G (IgG) or Postn-neutralizing antibody (Postn-nAb) was injected into injured muscle at 7 and 14 days after injury (dpi). We evaluated the effects of Postn-nAb on muscle repair after SMI.Results: The expression of Postn was dramatically upregulated after SMI. Compared with WT mice, Postn(-/-) mice had improved muscle recovery and attenuated fibrosis as well as a significantly reduced number of infiltrating fibroblasts. The proliferative potential of these fibroblasts in WT and Postn(-/-) mice was comparable at 14 dpi; however, the migration capability of fibroblasts was significantly enhanced in the presence of Postn (mean, 258%; 95% confidence interval, 183% to 334%). Moreover, the administration of Postn-nAb inhibited fibroblast infiltration and promoted muscle repair after SMI.Conclusions: Postn exacerbates fibrotic scar formation through the promotion of fibroblast migration into injured muscle after SMI. Treatment with Postn-nAb is effective for attenuating fibrosis and improving muscle recovery after SMI.