McLennan I S, Koishi K
Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand.
Dev Dyn. 1997 Feb;208(2):278-89. doi: 10.1002/(SICI)1097-0177(199702)208:2<278::AID-AJA14>3.0.CO;2-#.
Regeneration involves a number of cellular processes: revascularisation, invasion by haemopoietic cells, removal of necrotic tissue and finally reformation of the tissues. These processes have been extensively studied in vitro and are known to be affected by various growth factors. However, it has proven difficult to extrapolate the in vitro results to the in vivo situation. This is partially because the response of cells to growth factors is dependent on which other regulatory factors are present. The locations of various growth factors within regenerating skeletal muscles have been studied but information is not available for the transforming growth factor-beta2 (TGF-beta2) or TGF-beta3, even though the TGF-betas are putative regulators of revascularisation, inflammation and the formation of connective tissue and muscle fibres. In this paper, the cellular locations of TGF-beta2 and TGF-beta3 in freeze-lesioned skeletal muscle were examined using immunohistochemistry. The amounts and locations of the TGF-betas varied depending on the stage of degeneration/regeneration. The first isoform of TGF-beta to appear within the lesion was TGF-beta2, which accumulated at the junctions between the viable and necrotic portions of fibres. The production of TGF-beta2 by the damaged fibres occurred immediately prior to the inflammatory reaction. However, these two events are probably independent of each other as the TGF-beta2-rich necrotic tissue was not preferentially phagocytosed. The haemopoietic cells contained TGF-beta3 immunoreactivity and the lesioned area became progressively rich in TGF-beta3 as the macrophages accumulated in the lesion and removed the TGF-beta2-rich necrotic tissue. In vitro, the TGF-betas are potent inhibitors of myogenic fusion and have been postulated to control the onset of myotube formation in vivo. Consistent with this idea, the formation of myotubes did not occur until the TGF-beta3-positive haemopoietic cells had migrated from the ghosts of necrotic fibres. In contrast, fusing satellite cells and newly formed myotubes contained strong TGF-beta2 immunoreactivity. This observation, coupled with the recent report that satellite cells require functional TGF-beta receptors to fuse in vivo, suggests that TGF-beta2 may stimulate myotube formation in vivo.
血管再生、造血细胞浸润、坏死组织清除以及组织的最终重塑。这些过程已在体外得到广泛研究，并且已知会受到多种生长因子的影响。然而，已证明将体外实验结果外推至体内情况存在困难。部分原因在于细胞对生长因子的反应取决于其他哪些调节因子的存在。人们已经研究了再生骨骼肌中各种生长因子的定位，但关于转化生长因子-β2（TGF-β2）或TGF-β3的信息却不可得，尽管TGF-βs被认为是血管再生、炎症以及结缔组织和肌纤维形成的调节因子。在本文中，使用免疫组织化学方法检测了TGF-β2和TGF-β3在冷冻损伤骨骼肌中的细胞定位。TGF-βs的数量和定位因退变/再生阶段而异。在损伤部位最早出现的TGF-β同种型是TGF-β2，它在纤维的存活部分和坏死部分的交界处积累。受损纤维产生TGF-β2紧接在炎症反应之前。然而，这两个事件可能彼此独立，因为富含TGF-β2的坏死组织并未被优先吞噬。造血细胞含有TGF-β3免疫反应性，随着巨噬细胞在损伤部位积累并清除富含TGF-β2的坏死组织，损伤区域的TGF-β3逐渐增多。在体外，TGF-βs是成肌融合的有效抑制剂，并被推测在体内控制肌管形成的起始。与此观点一致的是，直到TGF-β3阳性造血细胞从坏死纤维的残骸中迁移出来，肌管才开始形成。相反，正在融合的卫星细胞和新形成 的肌管含有强烈的TGF-β2免疫反应性。这一观察结果，再加上最近关于卫星细胞在体内融合需要功能性TGF-β受体的报道，表明TGF-β2可能在体内刺激肌管形成。
