The Effect and Mechanism of KLF7 in the TLR4/NF-<i>κ</i>B/IL-6 Inflammatory Signal Pathway of Adipocytes

Zhang, Meixiu; Wang, Cuizhe; Wu, Jinxiu; Ha, Xiaodan; Deng, Yuchun; Zhang, Xueting; Wang, Jingzhou; Chen, Keru; Feng, Jiale; Zhu, Jiaojiao; Xie, Jingui; Zhang, Jun

doi:10.1155/2018/1756494

Cited by 35 publications

(42 citation statements)

References 27 publications

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“…Interestingly, according to String database [ 65 ], experimental data confirm the protein-by-protein interaction between SMAD4 and previously mentioned regulators RUNX2 , SOX9 , TEF3 , and NCOR1 . Finally, the list of regulators also includes TFs related to biological process like, inflammatory response ( NFE2L2 , KLF7 ) [ 66 , 67 ], hematopoiesis ( NFATC3 and IKZF2 ), cell-mediated immune response ( IKZF2 , IRF2 , NCOR1 , NFATC3 , RUNX2 , STAT1 , TCF4 ), humoral immune response ( IRF2 , NFATC3 , RUNX2 , STAT1 , TCF4 ), and the modulation of human B-cell differentiation ( KLF14 , KLF7 , MTA3 , STAT1 ) [ 68 ]. Therefore, in concordance with recent findings in human, mice, and pigs [ 5 , 39 , 69 ], our confirm that host-genome microbial interactions are mainly shaping by the host immune system.…”

Section: Discussionmentioning

confidence: 99%

A gene co-association network regulating gut microbial communities in a Duroc pig population

et al. 2021

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Background Analyses of gut microbiome composition in livestock species have shown its potential to contribute to the regulation of complex phenotypes. However, little is known about the host genetic control over the gut microbial communities. In pigs, previous studies are based on classical “single-gene-single-trait” approaches and have evaluated the role of host genome controlling gut prokaryote and eukaryote communities separately. Results In order to determine the ability of the host genome to control the diversity and composition of microbial communities in healthy pigs, we undertook genome-wide association studies (GWAS) for 39 microbial phenotypes that included 2 diversity indexes, and the relative abundance of 31 bacterial and six commensal protist genera in 390 pigs genotyped for 70 K SNPs. The GWAS results were processed through a 3-step analytical pipeline comprised of (1) association weight matrix; (2) regulatory impact factor; and (3) partial correlation and information theory. The inferred gene regulatory network comprised 3561 genes (within a 5 kb distance from a relevant SNP–P < 0.05) and 738,913 connections (SNP-to-SNP co-associations). Our findings highlight the complexity and polygenic nature of the pig gut microbial ecosystem. Prominent within the network were 5 regulators, PRDM15, STAT1, ssc-mir-371, SOX9 and RUNX2 which gathered 942, 607, 588, 284 and 273 connections, respectively. PRDM15 modulates the transcription of upstream regulators of WNT and MAPK-ERK signaling to safeguard naive pluripotency and regulates the production of Th1- and Th2-type immune response. The signal transducer STAT1 has long been associated with immune processes and was recently identified as a potential regulator of vaccine response to porcine reproductive and respiratory syndrome. The list of regulators was enriched for immune-related pathways, and the list of predicted targets includes candidate genes previously reported as associated with microbiota profile in pigs, mice and human, such as SLIT3, SLC39A8, NOS1, IL1R2, DAB1, TOX3, SPP1, THSD7B, ELF2, PIANP, A2ML1, and IFNAR1. Moreover, we show the existence of host-genetic variants jointly associated with the relative abundance of butyrate producer bacteria and host performance. Conclusions Taken together, our results identified regulators, candidate genes, and mechanisms linked with microbiome modulation by the host. They further highlight the value of the proposed analytical pipeline to exploit pleiotropy and the crosstalk between bacteria and protists as significant contributors to host-microbiome interactions and identify genetic markers and candidate genes that can be incorporated in breeding program to improve host-performance and microbial traits.

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Section: Discussionmentioning

confidence: 99%

A gene co-association network regulating gut microbial communities in a Duroc pig population

et al. 2021

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“…After TLR4 binds to its ligand, myeloid differentiation factor 88- (MyD88-)-dependent pathway was activated, after which NF-κB was activated via MyD88 and interleukin-1 receptor associated kinase (IRAK) to make p65 into the nucleus, and the downstream inflammatory factors IL-6 and TNF-α were transcriptionally activated. Finally the immune inflammatory response was triggered (Zhang et al, 2018). Activation of NF-κB further increased ROS through the pathways including cyclooxygenase activation, but did not increase the production of mitochondrial ROS (Jurk et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species Secreted by Leukocytes in Semen Induce Self-Expression of Interleukin-6 and Affect Sperm Quality

Shiyu

et al. 2020

Am J Mens Health

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Reproductive tract inflammation is considered an important cause of male infertility. Increased leukocytes in semen can produce many reactive oxygen species (ROS), which affect sperm function. The aim of this study is to identify the main source of ROS in seminal plasma and to assess the effect of ROS on leukocytes. Semen samples ( n = 20) with leukocyte concentration >1 × 106 were collected from a male infertility clinic. This study mainly compares the sperm function parameters of the normal group and the semen white blood cell group >1 × 106. The results identified that ROS in semen was closely related to sperm function parameters, and CD45+ leucocytes were the main source of ROS. Compared with the control group, the concentration of IL-2, IL-4, IL-6, IFN-γ, and TNF-α was higher in the experimental group. Leukocytes in semen may regulate the secretion of ROS through the mammalian target of rapamycin (mTOR) pathway. A considerable amount of ROS can upregulate the expression of IL-6 in leukocytes via the nuclear factor kappa-B (NF-kB) pathway.

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“…Activated NF-kB can enter the nucleus and either initiate or inhibit the transcription of related genes [29]. Inflammatory cytokine IL-6 plays an important role in the inflammatory, immune and stress response, which is regulated by NF-kB [30]. The results of Western Blot and qRT-PCR showed that the protein and mRNA levels of NF-kB and IL-6 significantly increased in the cerebral cortex after epilepsy, indicating that the NF-kB/ IL-6 signaling pathway is involved in the pathological process of epilepsy.…”

Section: Discussionmentioning

confidence: 99%

A study on the protective mechanism of mTOR inhibitor Everolimus on brain injury after epilepsy

Huang¹,

Hu²,

Zheng³

et al. 2020

Preprint

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Background: Epilepsy is a common acute and severe disease in infants and children. Recurrent seizures or status epilepticus can cause irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve) is an mammalian target of repamycin (mTOR) inhibitor that may affect neuronal excitability and have a therapeutic effect on epilepsy. Therefore, this study aimed to investigate the protective effect of Everolimus on post-epileptic brain injury and the regulation mechanism of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Intraperitoneal administration of kanic acid (KA) 15mg/kg was used to induce epilepsy in the developing rat and Everolimus (1, 2, 5mg/kg) was injected intraperitoneally 2 hours before KA injection. Cerebral cortex tissue was sampled at 24 hours post-epilepsy.Results: The protein and mRNA levels of PI3K、AKt、mTOR、NF-kB and IL-6 as well as microglia activation significantly increased after KA-induced epilepsy, however these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency. This study demonstrates that mTOR inhibitor.Conclusions: Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on post-epileptic brain damage.

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The Effect and Mechanism of KLF7 in the TLR4/NF-κB/IL-6 Inflammatory Signal Pathway of Adipocytes

Cited by 35 publications

References 27 publications

A gene co-association network regulating gut microbial communities in a Duroc pig population

A gene co-association network regulating gut microbial communities in a Duroc pig population

Reactive Oxygen Species Secreted by Leukocytes in Semen Induce Self-Expression of Interleukin-6 and Affect Sperm Quality

A study on the protective mechanism of mTOR inhibitor Everolimus on brain injury after epilepsy

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