Abstract
Skeletal muscle has an innate ability to restore damaged muscle fibers by contributing specific progenitor cells, called muscle satellite cells. Here we show that secretoglobin (SCGB) 3A1, a tumor suppressor gene in various malignancies including rhabdomyosarcoma, is induced just after muscle injury and contributes to damaged muscle fiber regeneration. Lineage tracing of SCGB3A1 in mice show that SCGB3A1-positive cells highly express myosin heavy chain (MyHC)-IIX in damaged fiber area. Scgb3a1-null and Pax7(CreERT2);Scgb3a1(f/f) conditional-null mice exhibit defective IIX and IIB fiber regeneration, with a concomitant reduction in the expression of Notch3, a gene important for the maintenance of satellite cell self-renewal pools. Aged Scgb3a1-null mice show reduced size of muscle fibers and mass, resulting in compromised muscle performance as compared to the age-matched wild-type mice. This study reveals that SCGB3A1 is an unexpected novel molecule expressed in muscle satellite cells that contributes to fiber type specific muscle regeneration.