Bradykinin‐mediated Ca<sup>2+</sup> signalling regulates cell growth and mobility in human cardiac c‐Kit<sup>+</sup> progenitor cells

Li, Gang; Che, Hui; Wu, Wei‐Yin; Jie, Ling‐Jun; Xiao, Guosheng; Wang, Yan

doi:10.1111/jcmm.13706

Cited by 11 publications

(13 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our previous studies have showed that hCPCs expressed B2 receptors but not B1 receptors, and treatment of hCPCs with BK promoted cell proliferation and migration by regulating Ca 2+ influx via the IP3 receptor and SOCE channel as well as the PLC/Akt/ERK pathway [11,12]. However, whether BK exerts an anti-apoptotic effect in vitro and whether transplantation of BKpreconditioned hCPCs in infarcted myocardium results in a significant increase in hCPC numbers and improves the left ventricular (LV) functional in vivo remain unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The tissue collection was approved by the Ethics Committee of Xiamen cardiovascular hospital with informed consent. The cell isolation protocol is the same as described previously [11][12][13]. Briefly, tissues were immediately transported in oxygenated cardioplegic, washed with cold phosphate buffer saline (PBS), and minced into 1-mm pieces.…”

Section: Isolation Of Human Cardiac C-kit + Progenitor Cellsmentioning

confidence: 99%

“…Western blotting was used to determine the expression of apoptosis-and autophagy-related proteins, such as pAkt, Akt, Bax, Bcl-2, caspase-3, cleaved caspase-3, LC3-I/II, Becline-1, ATG5, P62, and β-actin, with a different treatment on cultured hCPCs as described in previous studies [11][12][13][15][16][17]. Briefly, the cells were plated in 6-well plates in 2 mL IMDM medium with 1% FBS overnight and pretreated with different concentrations of BK (1, 3, and 10 nM) or 3-methyladenin (3MA) (10 μM) for 1 h and then treated with H 2 O 2 (500 μM) or rapamycin (10 μM) for additional 24 h. After treatment, cells were lysed by protein extraction radioimmunoprecipitation assay (RIPA) buffer (Solarbio, Beijing, China) with various protease inhibitors.…”

Section: Western Blottingmentioning

confidence: 99%

“…Bradykinin (BK) is a classic endogenous vasoactive peptide that protects cells against senescence or other damage by acting as a B2 receptor [9,10]. Our previous findings demonstrated that BK-mediated B2R activation promotes cell cycle progression and migration in hCPCs by regulating Ca 2+ via IP3R3 and SOCE channels as well as activating PLC, PKC, pERK1/2, pAkt, and cyclin D1 signaling pathway [11,12]. However, whether BK can protect of CPCs against H 2 O 2induced cell apoptosis and autophagy and whether transplantation of BK-pretreated-CPCs can improve myocardial infarction remain unknown and will be explored.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy

Zhou

Qiang

et al. 2021

Stem Cell Res Ther

Self Cite

View full text Add to dashboard Cite

Background Previous studies have demonstrated that human cardiac c-Kit+ progenitor cells (hCPCs) can effectively improve ischemic heart disease. However, the major challenge in applying hCPCs to clinical therapy is the low survival rate of graft hCPCs in the host heart, which limited the benefit of transplanted hCPCs. Bradykinin (BK) is a principal active agent of the tissue kinin-kallikrein system. Our previous studies have highlighted that BK mediated the growth and migration of CPCs by regulating Ca2+ influx. However, the protective effect of BK on CPCs, improvement in the survival rate of BK-pretreated hCPCs in the infarcted heart, and the related mechanism remain elusive. Methods HCPCs were treated with H2O2 to induce cell apoptosis and autophagy, and different concentration of BK was applied to rescue the H2O2-induced injury detected by MTT assay, TUNEL staining, flow cytometry, western blotting, and mitoSOX assays. The role of autophagy in the anti-apoptotic effect of BK was chemically activated or inhibited using the autophagy inducer, rapamycin, or the inhibitor, 3-methyladenine (3-MA). To explore the protective effect of BK on hCPCs, 3-MA or BK-pretreated hCPCs were transplanted into the myocardial infarcted rats. An echocardiogram was used to determine cardiac function, H&E and Masson staining were employed to assess pathological characteristics, HLA gene expression was quantified by qRT-PCR, and immunostaining was applied to examine neovascularization using confocal microscopy. Results The in vitro results showed that BK suppressed H2O2-induced hCPCs apoptosis and ROS production in a concentration-dependent manner by promoting pAkt and Bcl-2 expression and reducing cleaved caspase 3 and Bax expression. Moreover, BK restrained the H2O2-induced cell autophagy by decreasing LC3II/I, Beclin1, and ATG5 expression and increasing P62 expression. In the in vivo experiment, the transplanted BK- or 3-MA-treated hCPCs were found to be more effectively improved cardiac function by decreasing cardiomyocyte apoptosis, inflammatory infiltration, and myocardial fibrosis, and promoting neovascularization in the infarcted heart, compared to untreated-hCPCs or c-kit- cardiomyocytes (CPC- cells). Conclusions Our present study established a new method to rescue transplanted hCPCs in the infarcted cardiac area via regulating cell apoptosis and autophagy of hCPCs by pretreatment with BK, providing a new therapeutic option for heart failure.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Isolation Of Human Cardiac C-kit + Progenitor Cellsmentioning

confidence: 99%

Section: Western Blottingmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy

Zhou

Qiang

et al. 2021

Stem Cell Res Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“… 2015 ; Li et al. 2017 , 2018 ). After pre-treated antagonists for 1 h and incubated with different concentrations of con A (0.1, 0.3, 1, 3 μg/mL) for an additional 24 h, cells were harvested by 0.25% trypsin for flow cytometry analysis.…”

Section: Methodsmentioning

confidence: 99%

Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis

Zhou

Qiang

et al. 2021

Pharmaceutical Biology

Self Cite

View full text Add to dashboard Cite

Context Concanavalin A (Con A) exhibited multiple roles in cancer cells. However, the role of Con A in endothelial cells was not reported. Objective Our present study investigated the potential angiogenic role of Con A in endothelial cells and ischaemic hind-limb mice. Materials and methods Human umbilical vein endothelial cells and Ea.hy926 cells were employed to determine the effect of Con A (0.3, 1, and 3 μg/mL) or vehicle on angiogenesis and cell proliferation with tube formation, ELISA, flow cytometry, EdU, and western blot. Hind-limb ischaemic mice were conducted to determine the pro-angiogenic effect of Con A (10 mg/kg) for 7 days. Results Con A promoted tube formation to about three-fold higher than the control group and increased the secretion of VEGFa, PDGFaa, and bFGF in the medium. The cell viability was promoted to 1.3-fold by Con A 3 μg/mL, and cell cycle progression of G0G1 phase was decreased from 77% in the vehicle group to 70% in Con A 3 μg/mL, G2M was promoted from 15 to 19%, and S-phase was from 7 to 10%. Con A significantly stimulated phosphorylation of Akt and ERK1/2 and expression of cyclin D1 and decreased the expression of p27. These effects of Con A were antagonised by the PI3K inhibitor LY294002 (10 μM) and MEK pathway antagonist PD98059 (10 μM). Moreover, Con A (10 mg/kg) exhibited a repair effect in ischaemic hind-limb mice. Discussion and conclusions This study will provide a new option for treating ischaemic disease by local injection with Con A.

show abstract

Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis

Song,

Hu,

Hong

et al. 2024

Clinical & Translational Med

Self Cite

View full text Add to dashboard Cite

BackgroundAngiogenesis is critical for forming new blood vessels from antedating vascular vessels. The endothelium is essential for angiogenesis, vascular remodelling and minimisation of functional deficits following ischaemia. The insulin‐like growth factor (IGF) family is crucial for angiogenesis. Insulin‐like growth factor‐binding protein 5 (IGFBP5), a binding protein of the IGF family, may have places in angiogenesis, but the mechanisms are not yet completely understood. We sought to probe whether IGFBP5 is involved in pathological angiogenesis and uncover the molecular mechanisms behind it.Methods and resultsIGFBP5 expression was elevated in the vascular endothelium of gastrocnemius muscle from critical limb ischaemia patients and hindlimb ischaemic (HLI) mice and hypoxic human umbilical vein endothelial cells (HUVECs). In vivo, loss of endothelial IGFBP5 (IGFBP5EKO) facilitated the recovery of blood vessel function and limb necrosis in HLI mice. Moreover, skin damage healing and aortic ring sprouting were faster in IGFBP5EKO mice than in control mice. In vitro, the genetic inhibition of IGFBP5 in HUVECs significantly promoted tube formation, cell proliferation and migration by mediating the phosphorylation of IGF1R, Erk1/2 and Akt. Intriguingly, pharmacological treatment of HUVECs with recombinant human IGFBP5 ensued a contrasting effect on angiogenesis by inhibiting the IGF1 or IGF2 function. Genetic inhibition of IGFBP5 promoted cellular oxygen consumption and extracellular acidification rates via IGF1R‐mediated glycolytic adenosine triphosphate (ATP) metabolism. Mechanistically, IGFBP5 exerted its role via E3 ubiquitin ligase Von Hippel‐Lindau (VHL)‐regulated HIF1α stability. Furthermore, the knockdown of the endothelial IGF1R partially abolished the reformative effect of IGFBP5EKO mice post‐HLI.ConclusionOur findings demonstrate that IGFBP5 ablation enhances angiogenesis by promoting ATP metabolism and stabilising HIF1α, implying IGFBP5 is a novel therapeutic target for treating abnormal angiogenesis‐related conditions.

show abstract

Bradykinin‐mediated Ca²⁺ signalling regulates cell growth and mobility in human cardiac c‐Kit⁺ progenitor cells

Cited by 11 publications

References 58 publications

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy

Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis

Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis

Contact Info

Product

Resources

About

Bradykinin‐mediated Ca2+ signalling regulates cell growth and mobility in human cardiac c‐Kit+ progenitor cells

Cited by 11 publications

References 58 publications

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy

Pretreatment of cardiac progenitor cells with bradykinin attenuates H2O2-induced cell apoptosis and improves cardiac function in rats by regulating autophagy

Concanavalin A promotes angiogenesis and proliferation in endothelial cells through the Akt/ERK/Cyclin D1 axis

Deletion of endothelial IGFBP5 protects against ischaemic hindlimb injury by promoting angiogenesis

Contact Info

Product

Resources

About

Bradykinin‐mediated Ca²⁺ signalling regulates cell growth and mobility in human cardiac c‐Kit⁺ progenitor cells