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(American Journal of Pathology. 2002;161:1023-1031.)
© 2002 American Society for Investigative Pathology


Regular Articles

Expression of {alpha}7ß1 Integrin Splicing Variants during Skeletal Muscle Regeneration

Minna Kääriäinen*{dagger}, Liisa Nissinen{ddagger}, Stephen Kaufman§, Arnoud Sonnenberg, Markku Järvinen*{dagger}, Jyrki Heino{ddagger} and Hannu Kalimo||**

From the Medical School and the Institute of Medical Technology,* University of Tampere, Tampere, Finland; the Department of Surgery,{dagger} Section of Orthopaedics, Tampere University Hospital, Tampere, Finland; the Medicity Research Laboratory,{ddagger} Turku, Finland; the Department of Pathology,|| Turku University Hospital and University of Turku, Turku, Finland; the Paavo Nurmi Centre,** Turku, Finland; the Department of Cell and Structural Biology,§ University of Illinois, Urbana, Illinois; and the Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam, The Netherlands

Integrin {alpha}7ß1 is a laminin receptor, both subunits of which have alternatively spliced, developmentally regulated variants. In skeletal muscle ß1 has two major splice variants of the intracellular domain (ß1A and ß1D). {alpha}7X1 and {alpha}7X2 represent variants of the {alpha}7 ectodomain, whereas {alpha}7A and {alpha}7B are variants of the intracellular domain. Previously we showed that during early regeneration after transection injury of muscle {alpha}7 integrin mediates dynamic adhesion of myofibers along their lateral aspects to the extracellular matrix. Stable attachment of myofibers to the extracellular matrix occurs during the third week after injury, when new myotendinous junctions develop at the ends of the regenerating myofibers. Now we have analyzed the relative expression of ß1A/ß1D and {alpha}7A/{alpha}7B and {alpha}7X1/{alpha}7X2 isoforms during regeneration for 2 to 56 days after transection of rat soleus muscle using reverse transcriptase-polymerase chain reaction and immunohistochemistry. During early regeneration ß1A was the predominant isoform in both the muscle and scar tissue. Expression of muscle-specific ß1D was detected in regenerating myofibers from day 4 onwards, ie, when myogenic mitotic activity began to decrease, and it became more abundant with the progression of regeneration. {alpha}7B isoform predominated on day 2. Thereafter, the relative expression of {alpha}7A transcripts increased until day 7 with the concomitant appearance of {alpha}7A immunoreactivity on regenerating myofibers. Finally, {alpha}7B again became the predominant variant in highly regenerated myofibers. Similarly as in the controls, {alpha}7X1 and {alpha}7X2 isoforms were both expressed throughout the regeneration with a peak in {alpha}7X1 expression on day 4 coinciding with the dynamic adhesion stage. The results suggest that during regeneration of skeletal muscle the splicing of ß1 and {alpha}7 integrin subunits is regulated according to functional requirements. {alpha}7A and {alpha}7X1 appear to have a specific role during the dynamic phase of adhesion, whereas {alpha}7B, {alpha}7X2, and ß1D predominate during stable adhesion.





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