COLLAGEN AND STRETCH MODULATE AUTOCRINE SECRETION OF INSULIN-LIKE GROWTH-FACTOR-I AND INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS FROM DIFFERENTIATED SKELETAL-MUSCLE CELLS

Stretch-induced skeletal muscle growth may involve increased autocrine secretion of insulin-like growth factor-1 (IGF-1) since IGF-1 is a potent growth factor for skeletal muscle hypertrophy, and stretch elevates IGF-1 mRNA levels in vivo, In tissue cultures of differentiated avian pectoralis skeletal muscle cells, nanomolar concentrations of exogenous IGF-1 stimulated growth in mechanically stretched but not static cultures, These cultures released up to 100 pg of endogenously produced IGF-1/mu g of protein/day, as well as three major IGF binding proteins of 31, 36, and 43 kilodaltons (kDa), IGF-1 was secreted from both myofibers and fibroblasts coexisting in the muscle cultures, Repetitive stretch/relaxation of the differentiated skeletal muscle cells stimulated the acute release of IGF-1 during the first 4 h after initiating mechanical activity, but caused no increase in the long-term secretion over 24-72 h of IGF-1, or its binding proteins, Varying the intensity and frequency of stretch had no effect on the long-term efflux of IGF-1, In contrast to stretch, embedding the differentiated muscle cells in a three-dimensional collagen (Type I) matrix resulted in a 2-5-fold increase in long-term IGF-1 efflux over 24-72 h, Collagen also caused a 2-5-fold increase in the release of the IGF binding proteins, Thus, both the extracellular matrix protein type I collagen and stretch stimulate the autocrine secretion of IGF-1, but with different time kinetics, This endogenously produced growth factor may be important for the growth response of skeletal myofibers to both types of external stimuli.