The TG-interacting Factor TGIF1 Regulates Stress-induced Proinflammatory Phenotype of Endothelial Cells

Hneino, Mohammad; Blirando, Karl; Buard, Valérie; Tarlet, Georges; Benderitter, Marc; Hoodless, Pamela A.; François, Agnès; Milliat, Fabien

doi:10.1074/jbc.m112.388389

Cited by 19 publications

(13 citation statements)

References 35 publications

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“… 21 , 22 HIMECs (passage 4) and human umbilical vein endothelial cells (HUVECs) (passage 3) were transfected as described previously. 23 Briefly, cells were seeded into 6-well plates for 48 hours to reach 50%–70% confluence and were transfected with siRNA (100 nM) using Dharmafect according to the manufacturer’s protocols (Dharmacon, Chicago, IL). The antibiotic-free medium was replaced 48 hours after transfection and cells were irradiated and processed 4 days postirradiation for real-time PCR.…”

Section: Methodsmentioning

confidence: 99%

HIF-1α Deletion in the Endothelium, but Not in the Epithelium, Protects From Radiation-Induced Enteritis

Toullec¹,

Buard²,

Rannou

et al. 2018

Cellular and Molecular Gastroenterology and Hepatology

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Background & AimsRadiation therapy in the pelvic area is associated with side effects that impact the quality of life of cancer survivors. Interestingly, the gastrointestinal tract is able to adapt to significant changes in oxygen availability, suggesting that mechanisms related to hypoxia sensing help preserve tissue integrity in this organ. However, hypoxia-inducible factor (HIF)-dependent responses to radiation-induced gut toxicity are unknown. Radiation-induced intestinal toxicity is a complex process involving multiple cellular compartments. Here, we investigated whether epithelial or endothelial tissue-specific HIF-1α deletion could affect acute intestinal response to radiation.MethodsUsing constitutive and inducible epithelial or endothelial tissue-specific HIF-1α deletion, we evaluated the consequences of epithelial or endothelial HIF-1α deletion on radiation-induced enteritis after localized irradiation. Survival, radiation-induced tissue injury, molecular inflammatory profile, tissue hypoxia, and vascular injury were monitored.ResultsSurprisingly, epithelium-specific HIF-1α deletion does not alter radiation-induced intestinal injury. However, irradiated VECad-Cre+/-HIF-1αFL/FL mice present with lower radiation-induced damage, showed a preserved vasculature, reduced hypoxia, and reduced proinflammatory response compared with irradiated HIF-1αFL/FL mice.ConclusionsWe demonstrate in vivo that HIF-1α impacts radiation-induced enteritis and that this role differs according to the targeted cell type. Our work provides a new role for HIF-1α and endothelium-dependent mechanisms driving inflammatory processes in gut mucosae. Results presented show that effects on normal tissues have to be taken into account in approaches aiming to modulate hypoxia or hypoxia-related molecular mechanisms.

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Section: Methodsmentioning

confidence: 99%

HIF-1α Deletion in the Endothelium, but Not in the Epithelium, Protects From Radiation-Induced Enteritis

Toullec¹,

Buard²,

Rannou

et al. 2018

Cellular and Molecular Gastroenterology and Hepatology

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“…Studies have reported that TGIF can interact with Itch/AIP4 ubiquitin ligase to regulate TNF-a cytotoxicity, and that TNF-a can increase the stabilization of TGIF in a positive feedback loop (Demange et al 2009). In endothelial cells, TGIF regulates radiationand TNF-a-induced inflammation (Hneino et al 2012). In our preliminary results, TGIF was involved in the activation of the TBI-related proinflammatory cytokine IFN-c-treated mouse microglial cell line BV-2 as well as in ROS (reactive oxygen species) and TNF-a production (data not shown).…”

Section: Discussionmentioning

confidence: 81%

“…In endothelial cells, TGIF regulates radiation‐ and TNF‐α‐induced inflammation (Hneino et al . ). In our preliminary results, TGIF was involved in the activation of the TBI‐related proinflammatory cytokine IFN‐γ‐treated mouse microglial cell line BV‐2 as well as in ROS (reactive oxygen species) and TNF‐α production (data not shown).…”

Section: Discussionmentioning

confidence: 97%

Involvement of TG‐interacting factor in microglial activation during experimental traumatic brain injury

Chio

Chang

Lin

et al. 2014

Journal of Neurochemistry

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Traumatic brain injury (TBI) is a complex injury involving several physiological alterations, potentially leading to neurological impairment. Previous mouse studies using high-density oligonucleotide array analysis have confirmed the upregulation of transforming growth-interacting factor (TGIF) mRNA in TBI. TGIF is a transcriptional corepressor of transforming growth factor beta (TGF-b) signaling which plays a protective role in TBI. However, the functional roles of TGIF in TBI are not well understood. In this study, we used confocal microscopy after immunofluorescence staining to demonstrate the increase of TGIF levels in the activated microglia of the pericontusional cortex of rats with TBI. Intracerebral knockdown of TGIF in the pericontusional cortex significantly downregulated TGIF expression, attenuated microglial activation, reduced the volume of damaged brain tissue, and facilitated recovery of limb motor function. Collectively, our results indicate that TGIF is involved in TBI-induced microglial activation, resulting in secondary brain injury and motor dysfunction.

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“…In the present work, we used qPCR array to screen out 62 genes with significant differential expression (|fold regulation| > 2) associated with inflammatory reaction after X-ray irradiation. Including BCL2L1 , CARD6 , CASP1 , CASP5 , CCL2 , CCL7 , CD40LG , CXCL1 , CXCL2 , FADD , HSP90AA1 , HSP90B1 , IFNB1 , IFNG , IKBKG , IL12A , IL12B , IL18 , IL1B , IL6 , IRAK1 , IRF1 , MAP3K7 , MAPK12 , MAPK3 , MYD88 , NFKBIA , NLRP12 , NLRP3 , PTGS2 , SUGT1 , TNF , TNFSF11 , TNFSF14 , and TNFSF4 , 35 were associated with ionizing radiation response, as previously reported in different types of cells, tissues, and organisms [ 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. Among these genes, 27 (including AIM2 , CARD18 , CIITA , IL33 , IRF2 , MAPK11 , MAPK13 , MAPK9 , MEFV , NFKBIB , NLRC4 , NLRC5 , NLRP1 , NLRP4 , NLRP5 , NLRP6 , NLRX1 , NOD2 , P2RX7 , PANX1 , PEA15 , PSTPIP1 , PYDC1 , MOK , RIPK2 , TIRAP , and TXNIP ) have not previously been shown to be responsive to ionizing radiation damage at the mRNA level (|fold regulation| > 2).…”

Section: Resultsmentioning

confidence: 98%

“…Among 84 genes, 22 did not show any significant change in expression (the primers of these 22 genes were included in RT 2 Profiler PCR Arrays in 96-well plates). However, previous studies have shown that some of these genes, namely, BCL2 , BIRC2 , BIRC3 , CASP8 , CCL5 , CFLAR , CHUK , HSP90AB1 , IKBKB , MAPK8 , NAIP , NOD1 , NFKB1 , PYCARD , RELA , TRAF6 , and XIAP , exhibited significant expression changes at the mRNA level after irradiation [ 31 , 32 , 33 , 37 , 45 , 49 , 50 , 51 , 52 , 57 , 58 , 59 , 60 , 61 ]. Variations in radiation type, dose rate, tissue type, and cell types used in the different studies may account for the differences in results.…”

Section: Resultsmentioning

confidence: 99%

X-ray-Induced Changes in the Expression of Inflammation-Related Genes in Human Peripheral Blood

Wang

Guo

Han

et al. 2014

IJMS

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Using quantitative real-time polymerase chain reaction (PCR) array, we explored and compared the expression changes of inflammation-related genes in human peripheral blood irradiated with 0.5, 3, and 10 Gy doses of X-rays 24 h after exposure. Results indicated that the expression of 62 out of 84 genes was significantly altered after X-ray radiation. Among these 62 genes, 35 (such as TNFSF4) are known to be associated with radiation response, but others are novel. At a low radiation dose (0.5 Gy), 9 genes were up-regulated and 19 were down-regulated. With further increased dose to 3 Gy, 8 unique genes were up-regulated and 19 genes were down-regulated. We also identified 48 different genes that were differentially expressed significantly after 10 Gy of irradiation, and among these transcripts, up-regulated genes accounted for only one-third (16 genes) of the total. Of the 62 genes, 31 were significantly altered only at a specific dose, and a total of 10 genes were significantly expressed at all 3 doses. The dose- and time-dependent expression of CCL2 was confirmed by quantitative real-time reverse-transcription PCR. A number of candidate genes reported herein may be useful molecular biomarkers of radiation exposure in human peripheral blood.

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The TG-interacting Factor TGIF1 Regulates Stress-induced Proinflammatory Phenotype of Endothelial Cells

Cited by 19 publications

References 35 publications

HIF-1α Deletion in the Endothelium, but Not in the Epithelium, Protects From Radiation-Induced Enteritis

HIF-1α Deletion in the Endothelium, but Not in the Epithelium, Protects From Radiation-Induced Enteritis

Involvement of TG‐interacting factor in microglial activation during experimental traumatic brain injury

X-ray-Induced Changes in the Expression of Inflammation-Related Genes in Human Peripheral Blood

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