Knockdown of insulin-like growth factor 1 exerts a protective effect on hypoxic injury of aged BM-MSCs: role of autophagy

Yang, Ming; Wen, Tong-Chun; Chen, Haixu; Deng, Jingyu; Yang, Chao; Zhang, Zheng

doi:10.1186/s13287-018-1028-5

Cited by 37 publications

(25 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In human colorectal carcinoma drug-resistant cells, IGF-1 inhibited autophagy via Akt/mTOR pathway [ 67 ]. IGF-1 knockdown increased autophagy via reduction of Akt/mTOR in aged bone marrow mesenchymal stem cells (BM-MSCs) in hypoxic condition and protected cells against hypoxic injury [ 68 ]. This IGF-1-mediated autophagy reduction is suggested to be involved in cellular senescence and longevity.…”

Section: Muscle Protein Degradation: Autophagymentioning

confidence: 99%

Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy

Yoshida

Delafontaine

2020

Cells

348

209

View full text Add to dashboard Cite

Insulin-like growth factor-1 (IGF-1) is a key growth factor that regulates both anabolic and catabolic pathways in skeletal muscle. IGF-1 increases skeletal muscle protein synthesis via PI3K/Akt/mTOR and PI3K/Akt/GSK3β pathways. PI3K/Akt can also inhibit FoxOs and suppress transcription of E3 ubiquitin ligases that regulate ubiquitin proteasome system (UPS)-mediated protein degradation. Autophagy is likely inhibited by IGF-1 via mTOR and FoxO signaling, although the contribution of autophagy regulation in IGF-1-mediated inhibition of skeletal muscle atrophy remains to be determined. Evidence has suggested that IGF-1/Akt can inhibit muscle atrophy-inducing cytokine and myostatin signaling via inhibition of the NF-κΒ and Smad pathways, respectively. Several miRNAs have been found to regulate IGF-1 signaling in skeletal muscle, and these miRs are likely regulated in different pathological conditions and contribute to the development of muscle atrophy. IGF-1 also potentiates skeletal muscle regeneration via activation of skeletal muscle stem (satellite) cells, which may contribute to muscle hypertrophy and/or inhibit atrophy. Importantly, IGF-1 levels and IGF-1R downstream signaling are suppressed in many chronic disease conditions and likely result in muscle atrophy via the combined effects of altered protein synthesis, UPS activity, autophagy, and muscle regeneration.

show abstract

Section: Muscle Protein Degradation: Autophagymentioning

confidence: 99%

Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy

Yoshida

Delafontaine

2020

Cells

348

209

View full text Add to dashboard Cite

show abstract

“…Expression of hypoxia-inducible factor 1α also protects against Oxygen-Glucose deprivation via induction of autophagy and the PI3K/AKT/mTOR signaling pathway (43), while over-expression of CPT1C in human MSCs enhances survival via an increase in autophagic flux (49). In aging mice, knockdown of insulin-like growth factor-1 enhances survival of MSCs through autophagy and prolongs MSC survival in vivo (50). Taken together these studies clearly show that at least in some circumstances autophagy promotes MSC survival under stress.…”

Section: Msc Autophagy and Clinical Efficacymentioning

confidence: 99%

The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy

et al. 2019

View full text Add to dashboard Cite

Rapid progress is occurring in understanding the mechanisms underlying mesenchymal stromal cell (MSC)-based cell therapies (MSCT). However, the results of clinical trials, while demonstrating safety, have been varied in regard to efficacy. Recent data from different groups have shown profound and significant influences of the host inflammatory environment on MSCs delivered systemically or through organ-specific routes, for example intratracheal, with subsequent actions on potential MSC efficacies. Intriguingly in some models, it appears that dead or dying cells or subcellular particles derived from them, may contribute to therapeutic efficacy, at least in some circumstances. Thus, the broad cellular changes that accompany MSC death, autophagy, pre-apoptotic function, or indeed the host response to these processes may be essential to therapeutic efficacy. In this review, we summarize the existing literature concerning the necrobiology of MSCs and the available evidence that MSCs undergo autophagy, apoptosis, transfer mitochondria, or release subcellular particles with effector function in pathologic or inflammatory in vivo environments. Advances in understanding the role of immune effector cells in cell therapy, especially macrophages, suggest that the reprogramming of immunity associated with MSCT has a weighty influence on therapeutic efficacy. If correct, these data suggest novel approaches to enhancing the beneficial actions of MSCs that will vary with the inflammatory nature of different disease targets and may influence the choice between autologous or allogeneic or even xenogeneic cells as therapeutics.

show abstract

“…To mimic the ischaemic conditions in vitro, BM-MSCs were cultured under SD/H challenge. 18 In brief, when BM-MSCs reached 70%-80% confluence, the completed culture medium was changed to medium without foetal bovine serum (FBS) and then cultured under hypoxia (1% oxygen, 5% carbon dioxide and 94% nitrogen) for 48 hours. For haemin pre-treatment, BM-MSCs were cultured in complete medium with 10 µM haemin under normoxia (95% air and 5% carbon dioxide) for 24 hours prior to SD/H challenge.…”

Section: Serum Deprivation and Hypoxia (Sd/h)exposed Cell Culture Amentioning

confidence: 99%

Haemin pre‐treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

Deng

Liu

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

The cardiac protection of mesenchymal stem cell (MSC) transplantation for myocardial infarction (MI) is largely hampered by low cell survival. Haem oxygenase 1 (HO‐1) plays a critical role in regulation of cell survival under many stress conditions. This study aimed to investigate whether pre‐treatment with haemin, a potent HO‐1 inducer, would promote the survival of MSCs under serum deprivation and hypoxia (SD/H) and enhance the cardioprotective effects of MSCs in MI. Bone marrow (BM)‐MSCs were pretreated with or without haemin and then exposed to SD/H. The mitochondrial morphology of MSCs was determined by MitoTracker staining. BM‐MSCs and haemin‐pretreated BM‐MSCs were transplanted into the peri‐infarct region in MI mice. SD/H induced mitochondrial fragmentation, as shown by increased mitochondrial fission and apoptosis of BM‐MSCs. Pre‐treatment with haemin greatly inhibited SD/H‐induced mitochondrial fragmentation and apoptosis of BM‐MSCs. These effects were partially abrogated by knocking down HO‐1. At 4 weeks after transplantation, compared with BM‐MSCs, haemin‐pretreated BM‐MSCs had greatly improved the heart function of mice with MI. These cardioprotective effects were associated with increased cell survival, decreased cardiomyocytes apoptosis and enhanced angiogenesis. Collectively, our study identifies haemin as a regulator of MSC survival and suggests a novel strategy for improving MSC‐based therapy for MI.

show abstract

Knockdown of insulin-like growth factor 1 exerts a protective effect on hypoxic injury of aged BM-MSCs: role of autophagy

Cited by 37 publications

References 37 publications

Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy

Mechanisms of IGF-1-Mediated Regulation of Skeletal Muscle Hypertrophy and Atrophy

The Necrobiology of Mesenchymal Stromal Cells Affects Therapeutic Efficacy

Haemin pre‐treatment augments the cardiac protection of mesenchymal stem cells by inhibiting mitochondrial fission and improving survival

Contact Info

Product

Resources

About