Table 1 List of controversial studies on the role of MG53 in cardiomyopathy

Cao et al. [8]

MG53 KO mice with IPC model

The deficiency of MG53 exhibited myocardial vulnerability to ischemia/reperfusion injury and abolishes IPC protection

NO

Activation of PI3K-Akt-GSK3β pathway

Zhang, et al. [17]

MG53 KO mice with Post-conditioning model

PostC protected wt hearts against IR-induced MI, but failed to protect mg53-/- hearts.

NO

Activation of the RISK pathway

Song et al. [32]

HFD, Type II diabetes

Elevated MG53 leads to insulin resistance

YES

E3-ligase-mediated degradation of IRS-1

Ham et al. [61]

αMHC-MG53 TG mice

MG53 TG mice show cardiac hypotrophy at a young age, while exhibit cardiac hypertrophy at older age

Depends on age

E3-ligase-mediated degradation of IRS-1 and the associated Akt signal pathway

Liu et al. [46]

αMHC-MG53 TG mice

Cardiac hypertrophy and cardiomyopathy was induced by the overexpression of MG53.

YES

Regulating PPARα

Liu et al. [62]

MG53 KO mice, TAC

Deficiency of MG53 accelerated pressure overload-induced heart hypertrophy.

NO

Regulate KChIP2 by modulating NF-κB activity

Bian et al. [63]

tPA-MG53 TG mice

db/db mice

Mice with sustained elevation of MG53 in their bloodstream show normal glucose handling and lived a healthy lifespan.

NO

Enhanced tissue repair and regeneration

Wu et al. [47]

Diabetic db/db mice

Neutralizing circulating MG53 with monoclonal antibodies has therapeutic effects in db/db mice

YES

MG53 binds to the insulin receptor inhibiting the insulin signaling pathway

Wang et al. [60]

db/db mice

Gain or loss of MG53, and administration of rhMG53 did not altered insulin signaling and glucose handling

NO

N/A

Shan et al [18]

IPC, I/R model of mice

IPC induced secretion of MG53 and rhMG53 treatment are cardioprotective against I/R injury.

NO

Elevated activation of PKCδ

Philouze et al. [65]

MG53 KO mice, HFD

MG53 gene knock-down in muscle cells does not lead to impaired insulin response.

NO

N/A