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Cellular localisation of transforming growth factor‐beta 2 and ‐beta 3 (TGF‐β2, TGF‐β3) in damaged and regenerating skeletal muscles
Author(s) -
McLennan Ian S.,
Koishi Kyoko
Publication year - 1997
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/(sici)1097-0177(199702)208:2<278::aid-aja14>3.0.co;2-#
Subject(s) - transforming growth factor , biology , transforming growth factor beta , connective tissue , regeneration (biology) , growth factor , skeletal muscle , microbiology and biotechnology , tgf alpha , transforming growth factor, beta 3 , anatomy , biochemistry , receptor , genetics
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‐β2) or TGF‐β3, even though the TGF‐βs are putative regulators of revascularisation, inflammation and the formation of connective tissue and muscle fibres. In this paper, the cellular locations of TGF‐β2 and TGF‐β3 in freeze‐lesioned skeletal muscle were examined using immunohistochemistry. The amounts and locations of the TGF‐βs varied depending on the stage of degeneration/regeneration. The first isoform of TGF‐β to appear within the lesion was TGF‐β2, which accumulated at the junctions between the viable and necrotic portions of fibres. The production of TGF‐β2 by the damaged fibres occurred immediately prior to the inflammatory reaction. However, these two events are probably independent of each other as the TGF‐β2‐rich necrotic tissue was not preferentially phagocytosed. The haemopoietic cells contained TGF‐β3 immunoreactivity and the lesioned area became progressively rich in TGF‐β3 as the macrophages accumulated in the lesion and removed the TGF‐β2‐rich necrotic tissue. In vitro, the TGF‐βs 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‐β3‐positive haemopoietic cells had migrated from the ghosts of necrotic fibres. In contrast, fusing satellite cells and newly formed myotubes contained strong TGF‐β2 immunoreactivity. This observation, coupled with the recent report that satellite cells require functional TGF‐β receptors to fuse in vivo, suggests that TGF‐β2 may stimulate myotube formation in vivo. Dev. Dyn. 208:278–289, 1997. © 1997 Wiley‐Liss, Inc.