Enhanced Proliferation of Porcine Bone Marrow Mesenchymal Stem Cells Induced by Extracellular Calcium is Associated with the Activation of the Calcium‐Sensing Receptor and ERK Signaling Pathway

Ye, Jingjing; Ai, Wei; Zhang, Fenglin; Zhu, Xiaotong; Shu, Gang; Wang, Lina; Gao, Ping; Xi, Qianyun; Zhang, Yongliang; Jiang, Qingyan; Wang, Songbo

doi:10.1155/2016/6570671

Cited by 29 publications

(37 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The data were analyzed by MultiCycle for Windows software. Proliferation index (PI) = (S + G2/M)/(G0/G1 + S + G2/M) × 100% (Ye et al, ).…”

Section: Methodsmentioning

confidence: 99%

“…Approximately 5 × 10 4 PMECs were plated in 12‐well plates and subjected to 0, 10, and 600 µM of NaHS for 4 days, with six duplicate wells per group. The mRNA expression of Cyclin A2, Cyclin B1, Cyclin D3, Cyclin E2, P21, and PCNA were examined by real‐time quantitative PCR as previously described (Ye et al, ). Primer sequences (with their respective PCR fragment lengths) are shown in Table .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Zhang

Yuan

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

This study aimed to investigate the effects of exogenous H S on the proliferation of porcine mammary gland epithelial cells (PMECs) and explore the underlying mechanisms. We found that exposure of PMECs to NaHS, at concentrations ranging from 10 to 200 µM, stimulated cell proliferation. However, high concentration of NaHS (600 µM) inhibited PMECs proliferation. Accordingly, 10 µM NaHS significantly increased the percentage of cells undergoing DNA replication, elevated the mRNA and/or protein expression of Cyclin A2, Cyclin D1/3, Cyclin E2 and PCNA, and decreased p21 mRNA expression. In contrast, 600 µM NaHS elicited the opposite effects to that of 10 µM NaHS. In addition, PI3 K/Akt and mTOR signaling pathways were activated or inhibited in response to 10 or 600 µM NaHS, respectively. Furthermore, the promotion of PMECs proliferation, the change of proliferative genes expression, and the activation of mTOR signaling pathway induced by 10 µM NaHS were effectively blocked by PI3 K inhibitor Wortmannin. Similarly, inhibition of mTOR with Rapamycin totally abolished the 10 µM NaHS-induced stimulation of PMECs proliferation and alteration of proliferative genes expression, with no influence on PI3 K/Akt signaling pathway. Moreover, constitutive activation of Akt pathway via transfection of Akt-CA completely eliminated the inhibition of PMECs proliferation and mTOR signaling pathway, and the change of proliferative genes expression induced by 600 µM NaHS. In conclusion, our findings provided evidence that exogenous H S supplied by NaHS exerted biphasic effects on PMECs proliferation, with stimulation at lower doses and suppression at high dose, through the intracellular PI3 K/Akt-mTOR signaling pathway.

show abstract

“…The data were analyzed by MultiCycle for Windows software. Proliferation index (PI) = (S + G2/M)/(G0/G1 + S + G2/M) × 100% (Ye et al, ).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Zhang

Yuan

et al. 2018

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, ionomycininduced the increase of cytosolic Ca 2+ enhances the proliferation of primary mouse bone marrow mesenchymal stem cells (BMSCs) but not differentiation [32]. And high extracellular Ca 2+ promotes the proliferation of BMSCs via a calcium-sensing receptor and ERK signalling pathway [33]. However, several papers have reported that high extracellular Ca 2+ enhances adipogenesis probably through L-type Ca v channel [34] and calcium-sensing receptor [35] in porcine BMSCs.…”

Section: Calcium Signalling In Adipogenesismentioning

confidence: 99%

Involvement of calcium channels in the regulation of adipogenesis

Zhai

Yang

et al. 2020

Adipocyte

View full text Add to dashboard Cite

As an important second messenger in adipocytes, calcium ions (Ca 2+) are essential in regulating various intracellular signalling pathways that control critical cellular functions. Calcium channels show selective permeability to Ca 2+ and facilitate Ca 2+ entry into the cytoplasm, which are normally located in the plasmatic and intracellular membranes. The increase of cytosolic Ca 2+ modulates a variety of signalling pathways and results in the transcription of target genes that contribute to adipogenesis, a key cellular event includes proliferation and differentiation of adipocyte. In the past decades, the involvement of some Ca 2+-permeable ion channels, such as Ca 2+ release-activated Ca 2+ channels, transient receptor potential channels, voltage-gated calcium channels and others, in adipogenesis has been extensively explored. In the present review, we provided a summary of the expression and contributions of these Ca 2+-permeable channels in mediating Ca 2+ influxes that drive adipogenesis. Moreover, we discussed their potentials as future therapeutic targets.

show abstract

“…The protein of pBMSCs and iWAT was extracted and Western blot analysis was performed as previously described [25]. We used anti-PPARγ …”

Section: Western Blot Analysismentioning

confidence: 99%

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD)

Zhang

Meng

et al. 2018

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background/Aims: It has been implicated that calcium supplementation is involved in reducing body weight/fat and improving glucose homeostasis. However, the underlying mechanisms are still not fully understood. Here, we investigated the effects of calcium supplementation on adipogenesis and glucose homeostasis in porcine bone marrow mesenchymal stem cells (pBMSCs) and high fat diet (HFD)-fed mice and explored the involved signaling pathways. Methods: In vitro, pBMSCs were treated with 4 mM extracellular calcium ([Ca²⁺]_o) and/or 1 μM nifedipine, 0.1 μM BAPTA-AM, 1 μM KN-93, 50 nM wortmannin for 10 days. The intracellular calcium ([Ca²⁺]_i) levels were measured using Fluo 3-AM by flow cytometry. The adipogenic differentiation of pBMSCs was determined by Oil Red-O staining and triglyceride assay. The expression of marker genes involved in adipogenesis (peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)) and glucose uptake (glucose transporter 4 (GLUT4)), as well as the activation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and PI3K/Akt-FoxO1/AS160 signaling pathways were determined by Western blotting. Glucose uptake and utilization were examined using 2-NBDG assay and glucose content assay, respectively. In vivo, C57BL/6J male mice were fed a HFD (containing 1.2% calcium) without or with 0.6% (w/w) calcium chloride in drinking water for 13 weeks. The adipogenesis, glucose homeostasis and the involvement of CaMKII and PI3K/Akt signaling pathway were also assessed. Results: In vitro, [Ca²⁺]_o stimulated pBMSCs adipogenesis by increasing [Ca²⁺]_i level and activating CaMKII and PI3K/Akt-FoxO1 pathways. In addition, [Ca²⁺]_o promoted glucose uptake/utilization by enhancing AS160 phosphorylation, GLUT4 expression and translocation. However, the stimulating effects of [Ca²⁺]_o on pBMSCs adipogenesis and glucose uptake/utilization were abolished by L-VGCC blocker Nifedipine, [Ca²⁺]_i chelator BAPTA-AM, CaMKII inhibitor KN-93, or PI3K inhibitor Wortmannin. In vivo, calcium supplementation decreased body weight and fat content, increased adipocyte number, and improved glucose homeostasis, with elevated PPARγ and GLUT4 expression and PI3K/Akt activation in iWAT. Conclusion: calcium supplementation enhanced adipogenesis and glucose uptake in pBMSCs, which was coincident with the increased adipocyte number and improved glucose homeostasis in HFD-fed mice, and was associated with activation of CaMKII and PI3K/Akt-FoxO1/AS160 pathways. These data provided a broader understanding of the mechanisms underlying calcium-induced body weight/fat loss and glycemic control.

show abstract

Enhanced Proliferation of Porcine Bone Marrow Mesenchymal Stem Cells Induced by Extracellular Calcium is Associated with the Activation of the Calcium‐Sensing Receptor and ERK Signaling Pathway

Cited by 29 publications

References 44 publications

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Involvement of calcium channels in the regulation of adipogenesis

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD)

Contact Info

Product

Resources

About

Enhanced Proliferation of Porcine Bone Marrow Mesenchymal Stem Cells Induced by Extracellular Calcium is Associated with the Activation of the Calcium‐Sensing Receptor and ERK Signaling Pathway

Cited by 29 publications

References 44 publications

Exogenous H2S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Exogenous H2S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Involvement of calcium channels in the regulation of adipogenesis

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD)

Contact Info

Product

Resources

About

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway

Exogenous H₂S exerts biphasic effects on porcine mammary epithelial cells proliferation through PI3K/Akt‐mTOR signaling pathway