bims-stacyt Biomed news
on Starvation pathways leading to cytokine regulation
Issue of 2018‒05‒06
four papers selected by
Cristina Muñoz Pinedo
L’Institut d’Investigació Biomèdica de Bellvitge


  1. Oral Oncol. 2018 May;pii: S1368-8375(18)30089-7. [Epub ahead of print]80 23-32
    Joseph JP, Harishankar MK, Pillai AA, Devi A.
      Hypoxia, a condition of low oxygen tension in tissues, has emerged as a crucial factor in tumor pathophysiology. Hypoxic microenvironment gives rise to altered cellular metabolism and triggers varied molecular responses. These responses promote tumor progression and confer radiation resistance and chemo resistance to tumors. The predominant molecules that are associated with hypoxia research are the hypoxia inducible factors (HIFs). HIFs are known to regulate a large group of genes that are involved in cell survival, proliferation, motility, metabolism, pH regulation, extracellular matrix function, inflammatory cell recruitment and angiogenesis by inducing the expression of their downstream target genes. The process of epithelial to mesenchymal transition (EMT) has been associated with metastasis in cancer. Reports also suggest that hypoxia triggers EMT in several types of cancer including breast cancer, prostate cancer and oral cancer. Oral cancer is a predominant cancer in Central and South East Asia. However, in the recent times, the incidence rates of oral cancer have been increasing in Northern and Eastern Europe as well. This review articulates the role of hypoxia and the associated factors like HIFs in inducing EMT in oral cancer (OSCC).
    Keywords:  Epithelial to Mesenchymal Transition (EMT); Hypoxia; Hypoxia Inducible Factor (HIF); OSCC; Tumor progression
    DOI:  https://doi.org/10.1016/j.oraloncology.2018.03.004
  2. Cell Physiol Biochem. 2018 Apr 25. 46(5): 1807-1820
    Zhang T, Song N, Fang Y, Teng J, Xu X, Hu J, Zhang P, Chen R, Lu Z, Yu X, Ding X.
      BACKGROUND/AIMS: Even though delayed ischemic preconditioning (DIPC) has been reported to produce renal protection, the underlying mechanism remains poorly understood. We reported that a 15-minute renal ischemic preconditioning (IPC) 4 days before subsequent ischemia-reperfusion attenuated renal injury Kidney dendritic cells (DCs) are abundant in the renal tubulointerstitium and, depending on their status, can induce immune activation or tolerance. The aim of the present study was to investigate the role of DCs in IPC of the kidney.METHODS: Mouse kidneys were challenged by transient brief episodes of sublethal ischemia followed by subsequent prolonged ischemia. DC abundance and maturation in the spleen and kidney were measured by flow cytometry and immunohistochemical staining. To confirm the function of mature DCs in the renoprotective effect of IPC on renal ischemia-reperfusion injury the A2 adenosine receptor (A2AR) antagonist SCH58261 was administered to stimulate DC maturation prior to assessment of renal functional and histological injury and the inflammatory reaction.
    RESULTS: Compared with sham-operated animals, preconditioned mice had a reduced injury with less CD11c+ cells, lower levels of the pro-inflammatory cytokine IL-17 and reduced expression of the mature DC marker CCR7. Preconditioned mice also produced more of the anti-inflammatory cytokine IL-10. Both renal cells and splenocytes from these mice had more DCs (CD45+/CD11c+/F4/80-), but fewer of these DCs were mature (CD45+/CD11c+/ F4/80-/MHC-II+/CD80+) compared with those from sham-treated animals, suggesting that the immunomodulatory effect of renal ischemic preconditioning is both local and systemic. Additionally, injection of the A2AR antagonist SCH58261 reversed IPC-induced inhibition of DC maturation and mitigated the protective effect of preconditioning, suggesting that DC maturation contributes to immune cell-mediated ischemic preconditioning.
    CONCLUSION: Our results show that DIPC of the kidney provides local and systemic immunosuppression by inhibiting DC maturation and hence mediates a renal protective effect.
    Keywords:  Acute kidney injury; Delayed Ischemic Preconditioning; Dendritic cells; Ischemia–Reperfusion
    DOI:  https://doi.org/10.1159/000489366
  3. J Mol Neurosci. 2018 Apr 29.
    Yang Y, Cai Y, Zhang Y, Liu J, Xu Z.
      Adipose-derived stem cells (ADSCs) have been demonstrated to promote cerebral vascular remodeling processes after stroke. However, the exact molecular mechanism by which ADSCs exert protective roles in ischemic stroke is still poorly understood. In this study, we identified the role of exosomal microRNA-181b-5p (181b-Exos) in regulating post-stroke angiogenesis. The results of migration assay and capillary network formation assay showed that exosomes secreted by ADSCs (ADSCs-Exos) promoted the mobility and angiogenesis of brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD). Quantitative real-time polymerase chain reaction (qRT-PCR) showed that microRNA-212-5p (miR-212-5p) and miR-181b-5p were upregulated in BMECs subjected to the brain extract of the middle cerebral artery occlusion rats. The migration distance and tube length were increased in BMECs cultured with 181b-Exos. Furthermore, we identified that transient receptor potential melastatin 7 (TRPM7) was a direct target of miR-181b-5p. TRPM7 mRNA and protein levels were declined in BMECs cultured with 181b-Exos, but not in BMECs cultured with 212-Exos. Overexpression of TRPM7 reversed the effects of 181b-Exos on migration and tube formation of BMECs. In addition, 181b-Exos upregulated the protein expression of hypoxia-inducible factor 1α and vascular endothelial cell growth factor, and downregulated the protein expression of tissue inhibitor of metalloproteinase 3. The regulatory effect of 181b-Exos was attenuated by overexpressing TRPM7. Altogether, ADSCs-Exos promote the angiogenesis of BMECs after OGD via miR-181b-5p/TRPM7 axis, suggesting that ADSCs-Exos may represent a novel therapeutic approach for stroke recovery.
    Keywords:  Adipose-derived stem cells; Angiogenesis; Brain microvascular endothelial cells; Exosomes; MicroRNA-181b; Oxygen–glucose deprivation; TRPM7
    DOI:  https://doi.org/10.1007/s12031-018-1071-9
  4. Int J Biol Macromol. 2018 Apr 25. pii: S0141-8130(18)31087-0. [Epub ahead of print]
    Yu Y, Li J, Zhou H, Xiong Y, Wen Y, Li H.
      We investigated the transforming growth factor-b1 (TGF-β1)/Smad3 signaling pathway in rats with cerebral ischemia and oxygen-glucose-deprived (OGD) microglia. Cerebral ischemia is a clinical condition that occurs when insufficient blood flows to the brain to maintain metabolic activity. TGF-β1 is a well-known functional peptide that regulates cell differentiation, migration, proliferation, and apoptosis. In the current study, we determined the infarct size and TGF-β1/Smad3 protein expression in stroke-induced rats. Apoptosis and TGF-β1/Smad3 mRNA and protein expression were determined in transfected OGD human microglial cells. TGF-β1 treatment resulted in smaller infarct regions than in control cells, whereas TGF-β1 inhibitor treatment resulted in larger infarcts. The TGF-β1-treated groups showed substantial TGF-β1 and Smad3 expression by immunofluorescence compared to the controls. Apoptosis was significantly reduced in TGF-β1- and Smad3-transfected cells, and an increased rate of apoptosis was observed in Smad3 or TGF-β1 siRNA-transfected cells. TGF-β1 and Smad3 mRNA and protein expression increased following TGF-β1 and Smad3 transfection. Taken together, our experimental results show that Smad3 and TGF-β1 play a protective role against ischemic stroke, as demonstrated by the reduced infarct size. Smad3 and TGF-β1 expression was increased in cells transfected with TGF-β1, whereas Smad3 and TGF-β1 expression was increased in TGF-β1 inhibitor-transfected cells.
    Keywords:  Cytokines; Microglial cells; Smad3; TGF-β1; Transfection
    DOI:  https://doi.org/10.1016/j.ijbiomac.2018.04.113