Goetsch Sean C, Hawke Thomas J, Gallardo Teresa D, Richardson James A, Garry Daniel J
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8573, USA.
Physiol Genomics. 2003 Aug 15;14(3):261-71. doi: 10.1152/physiolgenomics.00056.2003.
Muscle regeneration is a complex process requiring the coordinated interaction between the myogenic progenitor cells or satellite cells, growth factors, cytokines, inflammatory components, vascular components and the extracellular matrix (ECM). Previous studies have elegantly described the physiological modulation of the regenerative process in response to muscle injury, but the molecular response that characterizes stages of the repair process remains ill-defined. The recent completion of the Human and Mouse Genome Projects and the advent of technologies such as high-density oligonucleotide array analysis facilitate an expanded analysis of complex processes such as muscle regeneration. In the present study, we define cellular and molecular events that characterize stages of muscle injury and regeneration. Utilization of transcriptional profiling strategies revealed coordinated expression of growth factors [i.e., Tgfb1, Igf1, Egf, chemokine (C-C motif) ligand 6 and 7], the fetal myogenic program (Myod1, Myf5, Myf6), and the biomatrix (procollagen genes, Mmp3, Mmp9, biglycan, periostin) during muscle regeneration. Corroboration of the transcriptional profiling analysis included quantitative real-time RT-PCR and in situ hybridization analyses of selected candidate genes. In situ hybridization studies for periostin [osteoblast-specific factor 2 (fasciclin I-like)] and biglycan revealed that these genes are restricted to mesenchymal derivatives during embryogenesis and are significantly regulated during regeneration of the injured hindlimb skeletal muscle. We conclude that muscle regeneration is a complex process that requires the coordinated modulation of the inflammatory response, myogenic progenitor cells, growth factors, and ECM for complete restoration of muscle architecture.
肌肉再生是一个复杂的过程，需要肌源性祖细胞或卫星细胞、生长因子、细胞因子、炎症成分、血管成分和细胞外基质（ECM）之间的协同相互作用。先前的研究已经很好地描述了再生过程对肌肉损伤的生理调节，但修复过程各阶段的分子反应仍不明确。人类和小鼠基因组计划的近期完成以及高密度寡核苷酸阵列分析等技术的出现，有助于对肌肉再生等复杂过程进行更广泛的分析。在本研究中，我们定义了表征肌肉损伤和再生阶段的细胞和分子事件。转录谱分析策略的应用揭示了生长因子[即转化生长因子β1（Tgfb1）、胰岛素样生长因子1（Igf1）、表皮生长因子（Egf）、趋化因子（C-C基序）配体6和7]、胎儿肌源性程序（Myod1、Myf5、Myf6）以及生物基质（前胶原基因、基质金属蛋白酶3（Mmp3）、基质金属蛋白酶9（Mmp9）、双糖链蛋白聚糖、骨膜蛋白）在肌肉再生过程中的协同表达。转录谱分析的佐证包括对选定候选基因的定量实时逆转录-聚合酶链反应（RT-PCR）和原位杂交分析。骨膜蛋白[成骨细胞特异性因子2（成束蛋白样）]和双糖链蛋白聚糖的原位杂交研究表明，这些基因在胚胎发育过程中仅限于间充质衍生物，并且在受伤后肢骨骼肌再生过程中受到显著调节。我们得出结论，肌肉再生是一个复杂的过程，需要对炎症反应、肌源性祖细胞、生长因子和细胞外基质进行协同调节，以实现肌肉结构的完全恢复。
