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Muscle repair: Making a good system better, faster; implications for aging, disease

d that deficiency in uPA pretty much eliminated muscle regeneration after injury. Muscles in animals without uPA showed no evidence of repair and little accumulation of macrophages, roaming cells that protect the body against foreign substances. PAI-1 deficient muscles showed "increased macrophage accumulation (and) the extent of macrophage accumulation correlated with both the clearance of (damaged) protein after injury and the efficiency of regeneration," according to the report.

Macrophage accumulation was impaired in injured muscle of uPA null mice and increased in PAI-1 null mice, compared to WT mice. At days three and five, macrophage accumulation in WT muscle was significantly greater than in uninjured control levels, while macrophage accumulation in PAI-1 null muscle was greater than in WT. Macrophage accumulation for uPA null mice was almost absent and significantly less than in WT mice.

Implications for aging and muscle diseases, and next steps

Koh noted that researchers are studying the role of the plasminogen system in repair of different tissues, including liver, lungs and the heart. The plasminogen system may be critical for efficient repair of many tissues and for minimizing scar formation.

Koh noted the following specific areas of interest:

* PAI-1 levels appear to increase with aging, and may explain, in part, the loss of repair capacity as we age. Koh plans to see whether manipulating PAI-1 levels can restore muscle repair in old muscles.

* PAI-1 levels also appear to be higher in muscle diseases like Duchenne Muscular Dystrophy. In such diseases, muscle repair processes can't keep up with the degeneration caused by the disease. The plasminogen system may represent a therapeutic target for improving muscle function in these instances.

* The plasminogen system likely has multiple roles in muscle repair. Understanding how the plasminogen system works in skeletal muscle may give some
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Source:American Physiological Society


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