Miranda Grounds - Academia.edu (original) (raw)

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Papers by Miranda Grounds

Experimental Cell Research, 2000

The expression of laminin isoforms and lamininbinding integrin receptors known to occur in muscle... more The expression of laminin isoforms and lamininbinding integrin receptors known to occur in muscle was investigated during myogenic regeneration after crush injury. Comparisons were made between dystrophic 129ReJ dy/dy mice, which have reduced laminin ␣2 expression, and their normal littermates. The overall histological pattern of regeneration after crush injury was similar in dy/dy and control muscle, but proceeded faster in dy/dy mice. In vitro studies revealed a greater yield of mononuclear cells extracted from dy/dy muscle and a reduced proportion of desmin-positive cells upon in vitro cultivation, reflecting the presence of inflammatory cells and "preactivated" myoblasts due to ongoing regenerative processes within the endogenous dystrophic lesions. Laminin ␣1 was not detectable in skeletal muscle. Laminin ␣2 was present in basement membranes of mature myofibers and newly formed myotubes in control and dy/dy muscles, albeit weaker in dy/dy. Laminin ␣2-negative myogenic cells were detected in dy/dy and control muscle, suggesting the involvement of other laminin ␣ chains in early myogenic differentiation, such as laminin ␣4 and ␣5 which were both transiently expressed in basement membranes of newly formed myotubes of dy/dy and control mice. Integrin ␤1 was expressed on endothelial cells, muscle fibers, and peripheral nerves in uninjured muscle and broadened after crush injury to the interstitium where it occurred on myogenic and nonmyogenic cells. Integrin ␣3 was not expressed in uninjured or regenerating muscle, while integrin ␣6 was expressed mainly on endothelial cells and peripheral nerves in uninjured muscle. Upon crush injury integrin ␣6 increased in the interstitium mainly on nonmyogenic cells, including infiltrating leukocytes, endothelial cells, and fibroblasts. In dy/dy muscle, integrin ␣6 occurred on some newly formed myotubes. Integrin ␣7 was expressed on muscle fibers at the myo-tendinous junction and showed weak and irregular expression on muscle fibers. After crush injury, integrin ␣7 expression extended to the newly formed myotubes and some myoblasts. However, many myoblasts and newly formed myotubes were integrin ␣7 negative. No marked difference was observed in integrin ␣7 expression between dy/dy and control muscle, either uninjured or after crush injury. Only laminin ␣4 and integrin ␣6 expression patterns were notably different between dy/dy and control muscle. Expression of both molecules was more extensive in dy/dy muscle, especially in the interstitium of regenerating areas and on newly formed myotubes. In view of the faster myogenic regeneration observed in dy/dy mice, the data suggest that laminin ␣4 and integrin ␣6 support myogenic regeneration. However, whether these accelerated myogenic effects are a direct consequence of the reduced laminin ␣2 expression in dy/dy mice, or an accentuation of the ongoing regenerative events in focal lesions in the muscle, requires further investigation.

Experimental Cell Research, 2000

The expression of laminin isoforms and lamininbinding integrin receptors known to occur in muscle... more The expression of laminin isoforms and lamininbinding integrin receptors known to occur in muscle was investigated during myogenic regeneration after crush injury. Comparisons were made between dystrophic 129ReJ dy/dy mice, which have reduced laminin ␣2 expression, and their normal littermates. The overall histological pattern of regeneration after crush injury was similar in dy/dy and control muscle, but proceeded faster in dy/dy mice. In vitro studies revealed a greater yield of mononuclear cells extracted from dy/dy muscle and a reduced proportion of desmin-positive cells upon in vitro cultivation, reflecting the presence of inflammatory cells and "preactivated" myoblasts due to ongoing regenerative processes within the endogenous dystrophic lesions. Laminin ␣1 was not detectable in skeletal muscle. Laminin ␣2 was present in basement membranes of mature myofibers and newly formed myotubes in control and dy/dy muscles, albeit weaker in dy/dy. Laminin ␣2-negative myogenic cells were detected in dy/dy and control muscle, suggesting the involvement of other laminin ␣ chains in early myogenic differentiation, such as laminin ␣4 and ␣5 which were both transiently expressed in basement membranes of newly formed myotubes of dy/dy and control mice. Integrin ␤1 was expressed on endothelial cells, muscle fibers, and peripheral nerves in uninjured muscle and broadened after crush injury to the interstitium where it occurred on myogenic and nonmyogenic cells. Integrin ␣3 was not expressed in uninjured or regenerating muscle, while integrin ␣6 was expressed mainly on endothelial cells and peripheral nerves in uninjured muscle. Upon crush injury integrin ␣6 increased in the interstitium mainly on nonmyogenic cells, including infiltrating leukocytes, endothelial cells, and fibroblasts. In dy/dy muscle, integrin ␣6 occurred on some newly formed myotubes. Integrin ␣7 was expressed on muscle fibers at the myo-tendinous junction and showed weak and irregular expression on muscle fibers. After crush injury, integrin ␣7 expression extended to the newly formed myotubes and some myoblasts. However, many myoblasts and newly formed myotubes were integrin ␣7 negative. No marked difference was observed in integrin ␣7 expression between dy/dy and control muscle, either uninjured or after crush injury. Only laminin ␣4 and integrin ␣6 expression patterns were notably different between dy/dy and control muscle. Expression of both molecules was more extensive in dy/dy muscle, especially in the interstitium of regenerating areas and on newly formed myotubes. In view of the faster myogenic regeneration observed in dy/dy mice, the data suggest that laminin ␣4 and integrin ␣6 support myogenic regeneration. However, whether these accelerated myogenic effects are a direct consequence of the reduced laminin ␣2 expression in dy/dy mice, or an accentuation of the ongoing regenerative events in focal lesions in the muscle, requires further investigation.