The Hsp70 Interacts With MAPK-activated Protein Kinase 2 To Regulate P38MAPK Stability And Myoblast Differentiation During Skeletal Muscle Regeneration

The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblast cells derived from muscle stem cells.Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration but the precise cellular mechanism remains elusive.Here we found that Hsp70 was upregulated during myoblast differentiation.Inhibition or depletion of Hsp70 impaired myoblast differentiation.Importantly,overexpression of p38MAPK,but not AKT,rescued the impairment of differentiation in Hsp70-depleted myoblasts.Hsp70 specifically regulated the stability of p38MAPK via modulating its substrate protein MK2.In vivo knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK levels in cardiotoxin-induced muscle regeneration.Hsp70 interacted with MK2 and is critical for maintained MK2-p38MAPK interaction in myoblasts.Functional analyses showed that MK2 promotes myoblast differentiation and muscle regeneration.Taken together,our finding reveals a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.