Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production

作者：Barton Elisabeth R; Park SooHyun; James Jose K; Makarewich Catherine A; Philippou Anastassios; Eletto Davide; Lei Hanqin; Brisson Becky; Ostrovsky Olga; Li Zihai; Argon Yair^*

来源：The FASEB Journal, 2012, 26(9): 3691-3702.

DOI：10.1096/fj.11-203026

• chaperones
• endocrine growth control
• glucose homeostasis
• glucose regulated protein 94
• IGFs

Insulin-like growth factors (IGFs) are critical for development and growth of skeletal muscles, but because several tissues produce IGFs, it is not clear which source is necessary or sufficient for muscle growth. Because it is critical for production of both IGF-I and IGF-II, we ablated glucose-regulated protein 94 (GRP94) in murine striated muscle to test the necessity of local IGFs for normal muscle growth. These mice exhibited smaller skeletal muscles with diminished IGF contents but with normal contractile function and no apparent endoplasmic reticulum stress response. This result shows that muscles rely on GRP94 primarily to support local production of IGFs, a pool that is necessary for normal muscle growth. In addition, body weights were similar to 30% smaller than those of litter-mate controls, and circulating IGF-I also decreased significantly, yet glucose homeostasis was maintained with little disruption to the growth hormone pathway. The growth defect was complemented on administration of recombinant IGF-I. Thus, unlike liver production of IGF-I, muscle IGF-I is necessary not only locally but also globally for whole-body growth.-Barton, E. R., Park, S., James, J. K., Makarewich, C. A., Philippou, A., Eletto, D., Lei, H., Brisson, B., Ostrovsky, O., Li, Z., Argon, Y. Deletion of muscle GRP94 impairs both muscle and body growth by inhibiting local IGF production. FASEB J. 26, 3691-3702 (2012). www.fasebj.org

• 出版日期2012-9