Blockade of IGF2R improves muscle regeneration and ameliorates Duchenne muscular dystrophy

Bella, Pamela; Farini, Andrea; Banfi, Stefania; Parolini, D.; Tonna, Noemi; Meregalli, Mirella; Belicchi, M.; Erratico, Silvia; D’Ursi, Pasqualina; Bianco, Fabio; Legato, Mariella; Ruocco, Chiara; Sitzia, Clementina; Sangiorgi, S.; Villa, Chiara; D’Antona, Giuseppe; Milanesi, Luciano; Nisoli, Enzo; Mauri, Pierluigi; Torrente, Yvan

doi:10.15252/emmm.201911019

Cited by 18 publications

(10 citation statements)

References 77 publications

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“…In our study, we found that IGF2R expression is increased in dystrophic muscles, and IGF2R and the store-operated Ca 2+ channel CD20 share a common hydrophobic binding motif stabilizing their association. We verified that the intravenous administration of an anti-IGF2R-neutralizing antibody facilitates IGF2/IGF1R interactions, while the occurrence of CD20 phosphorylation activation promotes the entrance of Ca 2+ ions into the sarcoplasm [63]. Based on this evidence, we proposed a signaling pathway to explain the activation of SERCA and the Ca 2+ flux through cells.…”

Section: Igf2r Modulates Vascular Remodeling and Skeletal Muscle Growthsupporting

confidence: 56%

Role of Insulin-Like Growth Factor Receptor 2 across Muscle Homeostasis: Implications for Treating Muscular Dystrophy

Torrente

Bella

Tripodi

et al. 2020

Cells

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The insulin-like growth factor 2 receptor (IGF2R) plays a major role in binding and regulating the circulating and tissue levels of the mitogenic peptide insulin-like growth factor 2 (IGF2). IGF2/IGF2R interaction influences cell growth, survival, and migration in normal tissue development, and the deregulation of IGF2R expression has been associated with growth-related disease and cancer. IGF2R overexpression has been implicated in heart and muscle disease progression. Recent research findings suggest novel approaches to target IGF2R action. This review highlights recent advances in the understanding of the IGF2R structure and pathways related to muscle homeostasis.

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Section: Igf2r Modulates Vascular Remodeling and Skeletal Muscle Growthsupporting

confidence: 56%

Role of Insulin-Like Growth Factor Receptor 2 across Muscle Homeostasis: Implications for Treating Muscular Dystrophy

Torrente

Bella

Tripodi

et al. 2020

Cells

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“…In adulthood, the expression of IGF2 is significantly suppressed; it mainly synthesizes in liver and transports to various parts of body. IGF2 has many conservative functions in mammals [ 3 , 4 , 5 , 6 , 7 ]. Its functions are mainly through the combination with insulin-like growth factor 1 receptor (IGF1R) and insulin-like growth factor 2 receptor (IGF2R), or it can compete with insulin-like growth factor binding protein (IGFBP).…”

Section: Introductionmentioning

confidence: 99%

Liver Expression of IGF2 and Related Proteins in ZBED6 Gene-Edited Pig by RNA-Seq

Zhao

Liu

et al. 2020

Animals

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Zinc finger BED-type containing 6 (ZBED6), a highly conservative transcription factor of placental mammals, has conservative interaction of insulin-like growth factor 2 (IGF2) based on the 16 bp binding sites of ZBED6 on the IGF2 sequence. IGF2 is related to embryo growth and cell proliferation. At the same time, its functions in muscle and adipose in mammals have been widely mentioned in recent studies. To further investigate the mechanism of ZBED6 on IGF2, we detected the expression of IGF2 and related genes in ZBED6 single allele knockout (ZBED6-SKO) pig tissues and analyzed the transcriptome of ZBED6-SKO pig liver. Through RNA-seq, we captured nine up-regulated genes and eight down-regulated genes which related to lipid metabolism. The results showed that the mRNA of IGF2 had an upward trend after the partial knockout of ZBED6 in liver and had no significant difference in protein expression of IGF2. In summary, ZBED6-SKO could affect the secretion of IGF2 in pig liver and its own lipid metabolism. Our research has provided basic information for revealing the regulatory mechanism of the interaction between ZBED6 and IGF2 in mammals.

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“…These studies show that Hsp72 stabilizes the SERCA pump and increases its activity in dystrophic muscles (Gehrig et al, 2012). A recent study shows that blocking the insulin-like growth factor 2 receptor activates SERCA function and enhances the Ca 2+ i removal in muscles of mdx mice (Bella et al, 2020).…”

Section: Enhancing Sr Ca 2+ Uptakementioning

confidence: 94%

Abnormal Calcium Handling in Duchenne Muscular Dystrophy: Mechanisms and Potential Therapies

et al. 2021

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Duchenne muscular dystrophy (DMD) is an X-linked muscle-wasting disease caused by the loss of dystrophin. DMD is associated with muscle degeneration, necrosis, inflammation, fatty replacement, and fibrosis, resulting in muscle weakness, respiratory and cardiac failure, and premature death. There is no curative treatment. Investigations on disease-causing mechanisms offer an opportunity to identify new therapeutic targets to treat DMD. An abnormal elevation of the intracellular calcium (Cai2+) concentration in the dystrophin-deficient muscle is a major secondary event, which contributes to disease progression in DMD. Emerging studies have suggested that targeting Ca2+-handling proteins and/or mechanisms could be a promising therapeutic strategy for DMD. Here, we provide an updated overview of the mechanistic roles the sarcolemma, sarcoplasmic/endoplasmic reticulum, and mitochondria play in the abnormal and sustained elevation of Cai2+ levels and their involvement in DMD pathogenesis. We also discuss current approaches aimed at restoring Ca2+ homeostasis as potential therapies for DMD.

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Blockade of IGF2R improves muscle regeneration and ameliorates Duchenne muscular dystrophy

Cited by 18 publications

References 77 publications

Role of Insulin-Like Growth Factor Receptor 2 across Muscle Homeostasis: Implications for Treating Muscular Dystrophy

Role of Insulin-Like Growth Factor Receptor 2 across Muscle Homeostasis: Implications for Treating Muscular Dystrophy

Liver Expression of IGF2 and Related Proteins in ZBED6 Gene-Edited Pig by RNA-Seq

Abnormal Calcium Handling in Duchenne Muscular Dystrophy: Mechanisms and Potential Therapies

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