The CCAAT/enhancer-binding protein delta/miR135a/thrombospondin 1 axis mediates PGE2-induced angiogenesis in Alzheimer's disease

Ko, Chiung Yuan; Chu, Yu; Narumiya, Shuh; Ying, Jhih; Furuyashiki, Tomoyuki; Aoki, Tomohiro; Wang, Shao Ming; Chang, Wen Chang; Wang, Ju Ming

doi:10.1016/j.neurobiolaging.2014.11.020

Cited by 33 publications

(28 citation statements)

References 90 publications

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“…Several studies have shown that NF-κB, CREB, and STAT3 are the upstream transcriptional activators of the C/EBPδ gene in various cell types [56–58]. In astrocytes, CREB has been suggested to play an important role in C/EBPδ transcription [59]. Among these three transcription factors, the activation of astrocytic NF-κB and STAT3 has been suggested to play important roles particularly in the upregulation of intermediate filaments, hypertrophy of the cell body, and glial scar formation after SCI [29, 60, 61].…”

Section: Discussionmentioning

confidence: 99%

Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury

Wang

Hsu

et al. 2015

Mol Neurobiol

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After spinal cord injury, inflammatory reaction induces the aggregation of astrocytes to form a glial scar that eventually blocks axonal regeneration. Transcription factor CCAAT/enhancer-binding protein delta (C/EBPδ) is a regulatory protein of genes responsive to inflammatory factors, but its role in glial scar formation after spinal cord injury remains unknown. By using a model of moderate spinal cord contusion injury at the mid-thoracic level, we found that C/EBPδ was expressed mostly in the reactive astrocytes bordering the lesion in wild-type mice from 7 days after the injury. C/EBPδ-deficient mice showed reduced glial scar formation, more residual white matter, and better motor function recovery compared with wild-type mice 28 days after the injury. Upon interleukin (IL)-1β stimulation in vitro, the increased expression of C/EBPδ in reactive astrocytes inhibited RhoA expression and, subsequently, the ability of astrocyte migration. However, these reactive astrocytes also produced an increased amount of matrix metalloproteinase-3, which promoted the migration of non-IL-1β-treated, inactive astrocytes. Although the involvement of other non-astroglial C/EBPδ cannot be entirely excluded, our studies suggest that astrocytic C/EBPδ is integral to the inflammatory cascades leading to glial scar formation after spinal cord injury.Electronic supplementary materialThe online version of this article (doi:10.1007/s12035-015-9486-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury

Wang

Hsu

et al. 2015

Mol Neurobiol

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“…In the AD brain, prostaglandin E2, an inflammatory messenger, reduces astrocytic expression of TSP1 by induction of miR-135 that targets the TSP1 mRNA. Binding of prostaglandin E2 to its receptor EP4 leads to protein kinase A (PKA)-dependent stimulation of the CCAAT/enhancer-binding protein δ (CEBPD), a transcriptional coactivator that up-regulates expression of miR-135 in astrocytes [ 183 ]. In summary, these findings suggest for a key role of TSP1 in astrogenesis and maturation, spine development, and synaptogenesis.…”

Section: Tsps In Other Pathologiesmentioning

confidence: 99%

Thrombospondins: A Role in Cardiovascular Disease

Chistiakov

Melnichenko

Myasoedova

et al. 2017

IJMS

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Thrombospondins (TSPs) represent extracellular matrix (ECM) proteins belonging to the TSP family that comprises five members. All TSPs have a complex multidomain structure that permits the interaction with various partners including other ECM proteins, cytokines, receptors, growth factors, etc. Among TSPs, TSP1, TSP2, and TSP4 are the most studied and functionally tested. TSP1 possesses anti-angiogenic activity and is able to activate transforming growth factor (TGF)-β, a potent profibrotic and anti-inflammatory factor. Both TSP2 and TSP4 are implicated in the control of ECM composition in hypertrophic hearts. TSP1, TSP2, and TSP4 also influence cardiac remodeling by affecting collagen production, activity of matrix metalloproteinases and TGF-β signaling, myofibroblast differentiation, cardiomyocyte apoptosis, and stretch-mediated enhancement of myocardial contraction. The development and evaluation of TSP-deficient animal models provided an option to assess the contribution of TSPs to cardiovascular pathology such as (myocardial infarction) MI, cardiac hypertrophy, heart failure, atherosclerosis, and aortic valve stenosis. Targeting of TSPs has a significant therapeutic value for treatment of cardiovascular disease. The activation of cardiac TSP signaling in stress and pressure overload may be therefore beneficial.

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“…In contrast, other studies have shown that miR-135a is an oncogenic miRNA in colorectal carcinomas ( Nagel et al, 2008 ) and that overexpression of miR-135a promoted tumorigenesis of portal vein tumor thrombus ( Liu et al, 2012 ) and enhanced the growth of HeLa- and NC104-E6/E7-derived tumor ( Leung et al, 2014 ). Studies have also shown that miR-135a is involved in brain inflammation and angiogenesis in Alzheimer’s disease ( Ko et al, 2015 ). In addition, it has been reported that miR-135a can promote proliferation and prevent apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…MiR-135a, a member of the miR-135 superfamily, has been reported to be involved in the tumorigenesis and act as a tumor suppressor ( Wu et al, 2012 ; Kroiss et al, 2015 ; Xu et al, 2016 ). MiR-135a expression in astrocytes has also been linked to brain inflammation and angiogenesis in Alzheimer’s disease ( Ko et al, 2015 ). Studies have also shown that miR-135a can promote proliferation and inhibit apoptosis of astrocytes in the bacterial meningitis rat models ( Dong et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-135a Protects Against Ethanol-Induced Apoptosis in Neural Crest Cells and Craniofacial Defects in Zebrafish by Modulating the Siah1/p38/p53 Pathway

Yuan

Yang

Fan

et al. 2020

Front. Cell Dev. Biol.

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MicroRNAs (miRNAs) are small non-coding RNAs that are involved in various biological processes, including apoptosis, by regulating gene expression. This study was designed to test the hypothesis that ethanol-induced downregulation of miR-135a contributes to ethanol-induced apoptosis in neural crest cells (NCCs) by upregulating Siah1 and activating the p38 mitogen-activated protein kinase (MAPK)/p53 pathway. We found that treatment with ethanol resulted in a significant decrease in miR-135a expression in both NCCs and zebrafish embryos. Ethanol-induced downregulation of miR-135a resulted in the upregulation of Siah1 and the activation of the p38 MAPK/p53 pathway and increased apoptosis in NCCs and zebrafish embryos. Ethanol exposure also resulted in growth retardation and developmental defects that are characteristic of fetal alcohol spectrum disorders (FASD) in zebrafish. Overexpression of miRNA-135a significantly reduced ethanol-induced upregulation of Siah1 and the activation of the p38 MAPK/p53 pathway and decreased ethanol-induced apoptosis in NCCs and zebrafish embryos. In addition, ethanol-induced growth retardation and craniofacial defects in zebrafish larvae were dramatically diminished by the microinjection of miRNA-135a mimics. These results demonstrated that ethanol-induced downregulation of miR-135a contributes to ethanol-induced apoptosis in NCCs by upregulating Siah1 and activating the p38 MAPK/p53 pathway and that the overexpression of miRNA-135a can protect against ethanol-induced apoptosis in NCCs and craniofacial defects in a zebrafish model of FASD.

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The CCAAT/enhancer-binding protein delta/miR135a/thrombospondin 1 axis mediates PGE2-induced angiogenesis in Alzheimer's disease

Cited by 33 publications

References 90 publications

Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury

Astrocytic CCAAT/Enhancer-Binding Protein Delta Contributes to Glial Scar Formation and Impairs Functional Recovery After Spinal Cord Injury

Thrombospondins: A Role in Cardiovascular Disease

MicroRNA-135a Protects Against Ethanol-Induced Apoptosis in Neural Crest Cells and Craniofacial Defects in Zebrafish by Modulating the Siah1/p38/p53 Pathway

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