Skeletal muscle-specific PGC-1α-b overexpression prevents eccentric contraction-induced muscle injury through an utrophin-independent pathway in mice.

Slower oxidative fibers are more resistant to eccentric contraction (ECC)-induced muscle damage than fast-twitch glycolytic fibers, but the mechanisms remain unclear. This study investigated the roles of the exercise-inducible PGC-1α isoform PGC-1α-b and utrophin in protecting against ECC-induced damage. ECCs were induced by supramaximal electrical stimulation of the left triceps surae in C57BL/6N wild-type (WT), PGC-1α-b transgenic (Tg), utrophin knockout (Utrn KO), and PGC-1α-b Tg/Utrn KO mice. Although the proportion of fast-type myosin heavy chain (MyHC) IIb in the gastrocnemius muscle was modestly lower in PGC-1α-b Tg and PGC-1α-b Tg/Utrn KO mice than in WT and Utrn KO mice, MyHC IIb remained the predominant isoform. At 3 days post injury (dpi), WT and Utrn KO mice exhibited reduced maximum isometric torque (MIT), Evans blue dye (EBD) staining in MyHC IIb-positive fibers, and calpain-1 activation. In contrast, PGC-1α-b Tg and PGC-1α-b Tg/Utrn KO mice showed substantial MIT recovery at 1 dpi and minimal EBD uptake and calpain-1 activation at 3 dpi. PGC-1α-b Tg muscles also preserved excitation-contraction coupling proteins and displayed increased mitochondrial markers and integrin α7B expression. Together, our findings suggest that PGC-1α-b confers resistance to ECC-induced muscle damage through a Utrn-independent mechanism.