M.Sc Thesis

M.Sc StudentSherbo Shay
SubjectThe Role of Stress-Induced C/EBP Homology Protein (CHOP)
in Muscle Regeneration
DepartmentDepartment of Medicine
Supervisor ASSOCIATE PROF. Eyal Bengal
Full Thesis textFull thesis text - English Version


Skeletal muscles are structured as contracting multi-nucleated fibers. The fiber is post mitotic. Attached to the fiber is a sub population of cells that are termed "satellite cells" (SC). The role of these cells is to provide progeny for myofiber repair.

When injured, SC function to rebuild the muscle but maintain a sufficient amount of SC in a quiescent state for future injury/regeneration events. Self-renewal of the SC pool is indispensable for the regeneration of the muscle. Failure of SC to fall back into quiescence and thus replenish the pool will most likely result in chronic damage to the muscle.

SC proceeds through several stages: activation, proliferation and differentiation. We hypothesize that the regeneration process occurs in a stressful environment affecting the fate of SC. CHOP, a member of the C/EBP family was shown in a previous work to be expressed in myoblasts undergoing differentiation in vitro.

In the present study, we analyzed the role of CHOP in skeletal muscle regeneration using a mouse model with acute muscle injury. We compared different aspects of muscle regeneration between CHOP KO and wild type mice. We detected that CHOP KO mice suffered from a delayed maturation of the newly formed muscle fibers. The delayed regeneration could be explained by a longer proliferation period of SC in CHOP KO mice than in wild type mice. Interestingly, when the muscle returns to homeostasis, the muscle tissue of CHOP KO mice have a larger population of SC relative to the wild type muscle tissue.

The regeneration process is dependent on an accurate inflammation process that involves macrophages of type M1 and M2. Initial analysis of inflammation indicates differences in the inflammatory response between wild type and knockout mice. Infiltration of macrophages to the damaged muscle occurred earlier in CHOP KO relative to wild type mice. Alteration in the inflammatory process may cause a shift in the balance between proliferation/differentiation of SC in favor of longer proliferation and delayed differentiation in CHOP KO mice.