scholarly journals IL-8 Enhances Therapeutic Effects of BMSCs on Bone Regeneration via CXCR2-Mediated PI3k/Akt Signaling Pathway

2018 ◽  
Vol 48 (1) ◽  
pp. 361-370 ◽  
Author(s):  
Aijun Yang ◽  
Yanzhu Lu ◽  
Junchao Xing ◽  
Zhilin Li ◽  
Xiaolong Yin ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Signaling Pathway ◽  
Bone Defect ◽  
Chondrogenic Differentiation ◽  
Akt Signaling ◽  
Host Cells ◽  
Therapeutic Effects ◽  
Akt Signaling Pathway

Background/Aims: Tissue engineering bone transplantation with bone marrow mesenchymal stem cells (BMSCs) is an effective technology to treat massive bone loss, while molecular regulation of the bone regeneration processes remains poorly understood. Here, we aimed to assess the role of interleukin-8 (IL-8) in the recruitment of host cells by seeded BMSCs and in the bone regeneration. Methods: A transwell assay was performed to examine the role of IL-8/CXCR1/CXCR2/PI3k/Akt on the migration potential of hBMSCs. The in vitro chondrogenic differentiation of hBMSCs was assessed by examination of 2 chondrogenic markers, Sox9 and type 2 collagen (COL2). mBMSCs were used in tissue engineered bone (TEB) with/without IL-8 implanted into bone defect area with CXCR2 or Akt inhibitors. Density and Masson staining of the regenerated bone were assessed. The chondrogenesis was assessed by expression levels of associated proteins, Sox9 and COL2, by RT-qPCR and by immunohistochemistry. Results: IL-8 may trigger in vitro migration of hBMSCs via CXCR2-mediated PI3k/Akt signaling pathway. IL-8 enhances osteogenesis in the TEB-implanted bone defect in mice. IL-8 induces chondrogenic differentiation of hBMSCs via CXCR2-mediated PI3k/Akt signaling pathway in vitro and in vivo. Conclusions: IL-8 enhances therapeutic effects of MSCs on bone regeneration via CXCR2-mediated PI3k/Akt signaling pathway.

scholarly journals Leptin-R and its association with PI3K/AKT signaling pathway in papillary thyroid carcinoma

2010 ◽  
Vol 17 (1) ◽  
pp. 191-202 ◽  
Author(s):  
Shahab Uddin ◽  
Prashant Bavi ◽  
Abdul K Siraj ◽  
Maqbool Ahmed ◽  
Maha Al-Rasheed ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Prognostic Marker ◽  
Disease Free Survival ◽  
Akt Signaling ◽  
Papillary Thyroid ◽  
Akt Signaling Pathway ◽  
Free Survival ◽  
Disease Free

The putative role of leptin and its receptor (Ob-R) in the pathogenesis of various primary human malignancies has been reported; however, their role in papillary thyroid cancer (PTC) has not yet been evaluated. We investigated the role of Ob-R in a large tissue microarray cohort of PTC followed by in vitro studies using a panel of PTC cell lines. Ob-R overexpression was seen in 80% PTCs and was significantly associated with poor disease-free survival (P=0.0235). PTCs that overexpressed Ob-R showed a aggressive phenotype characterized by older age, extrathyroid extension, larger tumor size, nodal metastasis, advanced stage, tall cell variant histological subtype, and a poor disease-free survival (P=0.0005, P=0.0006, P=0.0398, P=0.0004, P=0.0111, P=0.0003, and P=0.0235 respectively). However, Ob-R expression was not an independent prognostic marker to predict disease-free survival in multivariate analysis. PTCs with overexpression of Ob-R showed a significant direct association with overexpression of XIAP (P<0.0001) and Bcl-XL (P<0.0001). In vitro analysis showed that leptin stimulated cell proliferation and inhibited apoptosis via activation of phosphatidylinisitol 3′ kinase (PI3K)/protein kinase B (AKT) signaling pathway. Inhibition of PI3K activity by its inhibitor LY294002 abrogated leptin-mediated PI3K/AKT signaling. Gene silencing of Ob-R in PTC cells resulted in downregulation of phospho-AKT, Bcl-XL, and XIAP expression suggesting that leptin-mediated pathogenesis of PTC occurs via involvement of these downstream targets. Altogether, these data show that leptin plays an important role in PTC pathogenesis through PI3K/AKT pathway via Ob-R and is a potential prognostic marker associated with an aggressive phenotype and poor disease-free survival.

microRNA-382 suppresses the progression of pancreatic cancer through the PI3K/Akt signaling pathway by inhibition of Anxa3

2020 ◽  
Vol 319 (3) ◽  
pp. G309-G322
Author(s):  
Xiaohui Wan ◽  
Dongrui Guo ◽  
Qi Zhu ◽  
Rongfeng Qu
Keyword(s):  
Pancreatic Cancer ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Mesenchymal Transition ◽  
Node Metastasis

This study focused on the mechanism of miR-382 in epithelial mesenchymal transition and lymph node metastasis in PC in relation to Anxa3 and the PI3K/Akt signaling pathway. We found the inhibitory role of miR-382 in PC in vitro and in vivo.

scholarly journals In vivo and in vitro evidence of the neurotoxic effects of ropivacaine: The role of the Akt signaling pathway

2012 ◽  
Vol 6 (6) ◽  
pp. 1455-1459 ◽  
Author(s):  
ZHIHUA SUN ◽  
HUINING LIU ◽  
QULIAN GUO ◽  
XIAOPING XU ◽  
ZHONG ZHANG ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Neurotoxic Effects

scholarly journals Small Extracellular Vesicles Released from Bioglass/Hydrogel Scaffold Promote Vascularized Bone Regeneration by Transferring miR-23a-3p

2021 ◽  
Author(s):  
Hongxing Hu ◽  
Hang Zhang ◽  
Ziheng Bu ◽  
Mingmang Pan ◽  
Fang Lv ◽  
...  
Keyword(s):  
Bone Regeneration ◽  
Signaling Pathway ◽  
Bone Defect ◽  
Extracellular Vesicles ◽  
Critical Size ◽  
Akt Signaling ◽  
Potential Mechanism ◽  
Akt Signaling Pathway ◽  
Vascularized Bone

Abstract Background The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. MSCs-derived small extracellular vesicles (sEVs) show desirable therapeutic prospects in tissue regeneration due to satisfied advantages including high stability, facilitated acquisition and abundant source. However, the effect of Human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the potential mechanism of sEVs on the effects of osteogenesis and angiogenesis by luciferase reporter gene assay and western blot. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs(BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion This finds illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.

scholarly journals The Potential Role of CERS1 in Autophagy Through PI3K/AKT Signaling Pathway in Hypophysoma

2020 ◽  
Vol 19 ◽  
pp. 153303382097753
Author(s):  
Jingtao Wang ◽  
Jimin Zhang ◽  
Dongzhou Ma ◽  
Xiushan Li
Keyword(s):  
Signaling Pathway ◽  
Potential Role ◽  
Mrna Level ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Rt Pcr ◽  
Proliferation And Invasion

To explore the role and mechanism of CERS1 in hypophysoma and investigate whether CERS1 overexpression can change the autophagy process of hypophysoma, and then to explore whether CERS1’s effect was regulated by the PI3K/AKT signaling pathway. Western blot and RT-PCR were used to analyze the expression or mRNA level of CERS1 at different tissues or cell lines. Afterwards, the occurrence and development of hypophysoma in vivo and in vitro, respectively, was observed by using CERS1 overexpression by lentivirus. Finally, MK-2206 and LY294002 were applied to discuss whether the role of CERS1 was regulated by the PI3K/AKT signaling pathway. Results show that the CERS1 expression and mRNA level in tumor or AtT-20 cells were decreased. CERS1 over-expressed by lentivirus could inhibit hypophysoma development in vivo and in vitro by reducing tumor volume and weight, weakening tumor proliferation and invasion, and enhancing apoptosis. In addition, shCERS1 could reverse the process. The above results indicate that CERS1 is possibly able to enhance autophagy in hypophysoma through the PI3K/AKT signaling pathway.

scholarly journals Important Role of SDF-1/CXCR4 Axis in the Homing of Systemically Transplanted Human Amnion-Derived Mesenchymal Stem Cells (Had-Mscs) to Ovaries in Rats with Chemotherapy-Induced Premature Ovarian Insufficiency (POI)

2021 ◽  
Author(s):  
Li Ling ◽  
Jiying Hou ◽  
Dandan Liu ◽  
Dongyuan Tang ◽  
Yanqin Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathway ◽  
Ovarian Function ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Ovarian Insufficiency ◽  
Human Amnion ◽  
Cxcr4 Axis

Abstract Background: Chemotherapy can induce premature ovarian insufficiency (POI). POI causes multiple sequelae and is currently incurable. Our previous studies have demonstrated that systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) can home to chemotherapy-induced POI ovaries, and thus reduce ovarian injury and improve ovarian function in rats with POI. However, the cellular mechanisms that direct the migration and homing of hAD-MSCs to chemotherapy-induced POI ovaries are barely understood. This study was to investigate the role of SDF-1/CXCR4 axis in the migration and homing of systemically transplanted hAD-MSCs to chemotherapy-induced POI ovaries and its relevant downstream signaling pathways.Methods: CXCR4 expression in hAD-MSCs was tested by western blot and immunofluorescence assay. hAD-MSC migration was tested by transwell migration assay. SDF-1 level in rats was detected by ELISA. 72 of female SD rats were randomly divided into the control, POI, hAD-MSCs and hAD-MSCs+AMD3100 groups. POI rat models were established by intraperitoneal injection of cyclophosphamide. For the inhibitor treatment, hAD-MSCs were pretreated with AMD3100 before transplantation. hAD-MSCs labeled with PKH26 were injected into the tail vein of POI rats at 24 h after chemotherapy. After hAD-MSC transplantation, the homing of hAD-MSCs in ovaries, and ovarian function and pathological changes were examined. To further investigate molecular mechanisms, PI3K/Akt and ERK1/2 signaling pathways were detected. Results: hAD-MSCs expressed CXCR4. SDF-1 induced hAD-MSC migration in vitro. SDF-1 levels in ovaries and serum significantly increased in POI rats induced by chemotherapy, and POI ovaries attracted the homing of hAD-MSCs expressing CXCR4. The block of SDF-1/CXCR4 axis with AMD3100 can significantly reduce the number of hAD-MSCs homing to the POI ovaries, and further reduce their efficacy in POI treatment. The binding of SDF-1 to CXCR4 activated PI3K/Akt signaling pathway, and LY294002 significantly inhibited hAD-MSC migration induced by SDF-1 in vitro. Moreover, inhibition of PI3K/Akt signaling pathway significantly reduced the number of systemically transplanted hAD-MSCs homing to chemotherapy-induced POI ovaries in rats.Conclusions: SDF-1/CXCR4 axis partially mediates the migration and homing of systemically transplanted hAD-MSCs to chemotherapy-induced POI ovaries in rats, and PI3K/Akt signaling pathway might be involved in the migration and homing of hAD-MSCs mediated by SDF-1/CXCR4 axis.

scholarly journals MicroRNA expression profiling after recurrent febrile seizures in rat and emerging role of miR-148a-3p/SYNJ1 axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jian Xu ◽  
Mingqiang Sun ◽  
Xiaodong Li ◽  
Lei Huang ◽  
Zhenzhong Gao ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hippocampal Neurons ◽  
Target Genes ◽  
Expression Profiles ◽  
Neuronal Cell ◽  
Febrile Seizures ◽  
Akt Signaling ◽  
Akt Signaling Pathway

AbstractFebrile seizures (FSs) are common neurological disorders in both infants and children, although the precise underlying mechanism remains to be explored, especially in the expression pattern and function of microRNAs (miRNAs). In this report, we aimed to screen new potential miRNAs and examine the role of miR-148a-3p in hippocampal neurons in FS rats via Synaptojanin-1 (SYNJ1). Thirty rats were randomly divided into the normal and FS model groups, which were investigated by miRNA array. This process identified 31 differentially expressed (20 upregulated and 11 downregulated) miRNAs and potential miRNA target genes. In addition, hippocampal neurons were assigned into five groups for different transfections. Apoptosis was detected by TUNEL and flow cytometry. SYNJ1 was identified as a target gene of miR-148-3p. In vitro experiments revealed that inhibition of miR-148a-3p decreased neuronal cell apoptosis. Moreover, overexpression of miR-148a-3p resulted in activation of PI3K/Akt signaling pathway and the apoptosis of hippocampal neurons. MiR-148a-3p inhibitor could reverse the above events. Taken together, our data demonstrated that the hippocampal miRNA expression profiles of a rat model of FS provide a large database of candidate miRNAs and neuron-related target genes. Furthermore, miR-148a-3p acted as a apoptosis enhcaner via the activation of the SYNJ1/PI3K/Akt signaling pathway, highlighting a potential therapeutic target in the treatment of infants with hyperthermia-induced brain injury.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

scholarly journals Nobiletin enhances the development and quality of bovine embryos in vitro during two key periods of embryonic genome activation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karina Cañón-Beltrán ◽  
Yulia N. Cajas ◽  
Serafín Peréz-Cerezales ◽  
Claudia L. V. Leal ◽  
Ekaitz Agirregoitia ◽  
...  
Keyword(s):  
Embryonic Development ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Mitochondrial Activity ◽  
Bovine Embryos ◽  
Akt Signaling Pathway ◽  
Cell Stage ◽  
Development In Vitro

AbstractIn vitro culture can alter the development and quality of bovine embryos. Therefore, we aimed to evaluate whether nobiletin supplementation during EGA improves embryonic development and blastocyst quality and if it affects PI3K/AKT signaling pathway. In vitro zygotes were cultured in SOF + 5% FCS (Control) or supplemented with 5, 10 or 25 µM nobiletin (Nob5, Nob10, Nob25) or with 0.03% dimethyl-sulfoxide (CDMSO) during minor (2 to 8-cell stage; MNEGA) or major (8 to 16-cell stage; MJEGA) EGA phase. Blastocyst yield on Day 8 was higher in Nob5 (42.7 ± 1.0%) and Nob10 (44.4 ± 1.3%) for MNEGA phase and in Nob10 (61.0 ± 0.8%) for MJEGA phase compared to other groups. Mitochondrial activity was higher and lipid content was reduced in blastocysts produced with nobiletin, irrespective of EGA phase. The mRNA abundance of CDK2, H3-3B, H3-3A, GPX1, NFE2L2 and PPARα transcripts was increased in 8-cells, 16-cells and blastocysts from nobiletin groups. Immunofluorescence analysis revealed immunoreactive proteins for p-AKT forms (Thr308 and Ser473) in bovine blastocysts produced with nobiletin. In conclusion, nobiletin supplementation during EGA has a positive effect on preimplantation bovine embryonic development in vitro and corroborates on the quality improvement of the produced blastocysts which could be modulated by the activation of AKT signaling pathway.

Role of Akt signaling pathway regulation in the speckled mousebird (Colius striatus) during torpor displays tissue specific responses

2020 ◽  
Vol 75 ◽  
pp. 109763
Author(s):  
Stuart R. Green ◽  
Rasha Al-Attar ◽  
Andrew E. McKechnie ◽  
Samantha Naidoo ◽  
Kenneth B. Storey
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Tissue Specific ◽  
Pathway Regulation
Sign in / Sign up

Export Citation Format

Share Document