The regenerative process of injured muscle is dependent on the fusion and differentiation of myoblasts derived from muscle stem cells. Hsp70 is important for maintaining skeletal muscle homeostasis and regeneration, but the precise cellular mechanism remains elusive. In this study, we found that Hsp70 was upregulated during myoblast differentiation. Depletion or inhibition of Hsp70/Hsc70 impaired myoblast differentiation. Importantly, overexpression of p38 mitogen-activated protein kinase α (p38MAPKα) but not AKT1 rescued the impairment of myogenic differentiation in Hsp70- or Hsc70-depleted myoblasts. Moreover, Hsp70 interacted with MK2, a substrate of p38MAPK, to regulate the stability of p38MAPK. Knockdown of Hsp70 also led to downregulation of both MK2 and p38MAPK in intact muscles and during cardiotoxin-induced muscle regeneration. Hsp70 bound MK2 to regulate MK2-p38MAPK interaction in myoblasts. We subsequently identified the essential regions required for Hsp70-MK2 interaction. Functional analyses showed that MK2 is essential for both myoblast differentiation and skeletal muscle regeneration. Taken together, our findings reveal a novel role of Hsp70 in regulating myoblast differentiation by interacting with MK2 to stabilize p38MAPK.
This paper presents a perturbative analysis of bifurcation pressure of 2D corroded rings characterized by locally thinned regions under external pressure by asymptotically analyzing the Timoshenko differential equation and parametric analysis. First, for the case of one corrosion region, we formulate regular perturbative solution separately for anti-symmetric bifurcation and symmetric bifurcation cases. Concise formulation is presented by introducing a corrosion severity parameter and perturbative solution is presented. Second, we present a detailed analysis for the case where corrosion region has small angular extent by converting it into a singular perturbative problem and conduct various asymptotic analyses to illustrate the interesting interlacing behaviors. The derived explicit formula explains some numerical observation by Fatt in literature. Third, we conduct parametric analysis for the case of two interacting corrosion regions by classifying it into two cases: symmetric corrosion case and non-symmetric corrosion case. Finally, we present asymptotical analysis to investigate the extremely corroded case and show by Prufer transformation that anti-symmetric bifurcation pressure decreases when the distance of two corrosion regions is increasing. This paper serves to enhance the understanding of the collapse pressure of subsea pipes with local thickness reduction.
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