Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy

Deng, Jingyu; Yang, Chao; Wang, Yong; Yang, Ming; Chen, Haixu; Ning, Hongjuan; Wang, Chengzhu; Liu, Yanjun; Zhang, Zheng; Hu, Taohong

doi:10.1186/s13287-019-1256-3

Cited by 29 publications

(22 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, H/SD in vitro cellular model was performed to mimic the in vivo ischemic environment (34) . Concurrently, our results revealed that H/SD injury reduced cells survival and caused paracrine dysfunction of BM-MSCs (12) . Thus, promoting the low viability of BM-MSCs under hypoxic conditions after transplantation is crucial for elevating the e ciency of cellular therapy.…”

Section: Discussionsupporting

confidence: 67%

“…Isolation, culture and treatments of BM-MSCs BM-MSCs were isolated and expanded as described (12) . Brie y, bone marrow was ushed from the femoral and tibia of adult Tg ( uc -egfp) mice with fetal bovine serum (FBS)-free Dulbecco's modi ed Eagle's medium (DMEM).…”

Section: Animalmentioning

confidence: 99%

“…However, many studies have shown that only a small number of transplanted MSCs eventually survive to play protective effects (9)(10)(11) . Also, evidences indicated that under myocardial ischemia conditions, hypoxic stress caused increased apoptosis of MSCs and reduce its therapeutic effects (1,12) . Therefore, it is reasonable to assume that promoting the low engrafted MSCs survival in ischemia myocardial tissue may be the key to improving stem cells therapeutic e cacy after MI.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Deng

Zhang

Wang

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

show abstract

Section: Discussionsupporting

confidence: 67%

Section: Animalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Deng

Zhang

Wang

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Delayed platelet aggregation in Ip6k1-KO mice [183] is beneficial in thromboembolism, but may delay clotting in normal subjects. IP6K1 inhibits Akt in metabolic cells and tissues [12,29,40,[42][43][44][45]238]. In young, chow-fed tissues, IP6K1-disruption minimally alters Akt [22,29], whereas its perturbation reduces high fat diet or age induced Akt inhibition.…”

Section: Potential Risks Of Targeting the Ip6k Pathway In Metabolic Dmentioning

confidence: 99%

Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases

2020

View full text Add to dashboard Cite

In mammals, a family of three inositol hexakisphosphate kinases (IP6Ks) synthesizes the inositol pyrophosphate 5-IP7 from IP6. Genetic deletion of Ip6k1 protects mice from high fat diet induced obesity, insulin resistance and fatty liver. IP6K1 generated 5-IP7 promotes insulin secretion from pancreatic β-cells, whereas it reduces insulin signaling in metabolic tissues by inhibiting the protein kinase Akt. Thus, IP6K1 promotes high fat diet induced hyperinsulinemia and insulin resistance in mice while its deletion has the opposite effects. IP6K1 also promotes fat accumulation in the adipose tissue by inhibiting the protein kinase AMPK mediated energy expenditure. Genetic deletion of Ip6k3 protects mice from age induced fat accumulation and insulin resistance. Accordingly, the pan IP6K inhibitor TNP [N2-(m-trifluorobenzyl), N6-(p-nitrobenzyl)purine] ameliorates obesity, insulin resistance and fatty liver in diet induced obese mice by improving Akt and AMPK mediated insulin sensitivity and energy expenditure. TNP also protects mice from bone loss, myocardial infarction and ischemia reperfusion injury. Thus, the IP6K pathway is a potential target in obesity and other metabolic diseases. Here, we summarize the studies that established IP6Ks as a potential target in metabolic diseases. Further studies will reveal whether inhibition of this pathway has similar pleiotropic benefits on metabolic health of humans.

show abstract

“…Isolation, culture and treatments of BM-MSCs BM-MSCs were isolated and expanded as described (10) . Briefly, bone marrow was flushed from the femoral and tibia of adult Tg(fluc -egfp) mice with fetal bovine serum (FBS)-free Dulbecco's modified Eagle's medium (DMEM).…”

Section: Introductionmentioning

confidence: 99%

FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Deng

Zhang

Wang

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc + –eGFP + ) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and FNDC5 +/+ in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5 +/+ . Results Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5 +/+ alleviated these injuries. Longitudinal in vivo bioluminescence imaging illustrated that MSCs FNDC5+/+ treatment improved the survival of transplanted MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo . Furthermore, MSCs FNDC5+/+ therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.

show abstract

Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy

Cited by 29 publications

References 46 publications

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Targeting the Inositol Pyrophosphate Biosynthetic Enzymes in Metabolic Diseases

FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction

Contact Info

Product

Resources

About