scholarly journals Roles of tumour necrosis factor-related weak inducer of apoptosis/fibroblast growth factor-inducible 14 pathway in lupus nephritis

Nephrology ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 101-106 ◽  
Author(s):  
Jingyun Chen ◽  
Linlin Wei ◽  
Yumin Xia
Keyword(s):  
Growth Factor ◽  
Lupus Nephritis ◽  
Fibroblast Growth Factor ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Fibroblast Growth ◽  
Necrosis Factor

scholarly journals Tumor Necrosis Factor Receptor Mediates Fibroblast Growth Factor-Inducible 14 Signaling

2017 ◽  
Vol 43 (2) ◽  
pp. 579-588 ◽  
Author(s):  
Xuening Wang ◽  
Shengxiang Xiao ◽  
Yumin Xia
Keyword(s):  
Growth Factor ◽  
Tumor Necrosis Factor ◽  
Fibroblast Growth Factor ◽  
Tumor Necrosis ◽  
Expression Profiles ◽  
Tumor Necrosis Factor Receptor ◽  
Fibroblast Growth ◽  
Cell Fates ◽  
Apoptosis Protein ◽  
Necrosis Factor

Tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) engages its sole receptor, fibroblast growth factor–inducible 14 (Fn14), which participates in various inflammatory and immunologic processes. TWEAK/Fn14 interaction induces different cell fates depending on the local microenvironment, which correlates with certain expression profiles of TNF receptors (TNFR). The predominant expression of TNFR1 or TNFR2 facilitates cell death or proliferation, respectively, on TWEAK/Fn14 activation. TNFR-associated factors (TRAF) interact with Fn14, cellular inhibitor of apoptosis protein (cIAP)-1, and TNFR, consequently transducing signals from TWEAK to downstream cytokines and cell cycle mediators. An Fn14-TRAF2-TNFR axis has been suggested in the function of TWEAK/Fn14 signaling, which may serve as a target in the development of novel therapeutic strategies for many diseases that have Fn14-overexpressing cells in affected tissues. The aims of this review are: 1) to present the main results on TWEAK/Fn14 regulation of cell fates, 2) to analyze the mechanism of the Fn14-TRAF2-TNFR axis, and 3) to summarize the potential strategies in the pharmacologic targeting of this axis.

scholarly journals Two waves of transcriptomic changes in periovulatory human granulosa cells

2020 ◽  
Vol 35 (5) ◽  
pp. 1230-1245 ◽  
Author(s):  
L C Poulsen ◽  
J A Bøtkjær ◽  
O Østrup ◽  
K B Petersen ◽  
C Yding Andersen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Fertility Treatment ◽  
Protein Coding ◽  
Time Points ◽  
Protein Coding Genes ◽  
Upstream Regulators ◽  
Necrosis Factor

Abstract STUDY QUESTION How does the human granulosa cell (GC) transcriptome change during ovulation? SUMMARY ANSWER Two transcriptional peaks were observed at 12 h and at 36 h after induction of ovulation, both dominated by genes and pathways known from the inflammatory system. WHAT IS KNOWN ALREADY The crosstalk between GCs and the oocyte, which is essential for ovulation and oocyte maturation, can be assessed through transcriptomic profiling of GCs. Detailed transcriptional changes during ovulation have not previously been assessed in humans. STUDY DESIGN, SIZE, DURATION This prospective cohort study comprised 50 women undergoing fertility treatment in a standard antagonist protocol at a university hospital-affiliated fertility clinic in 2016–2018. PARTICIPANTS/MATERIALS, SETTING, METHODS From each woman, one sample of GCs was collected by transvaginal ultrasound-guided follicle aspiration either before or 12 h, 17 h or 32 h after ovulation induction (OI). A second sample was collected at oocyte retrieval, 36 h after OI. Total RNA was isolated from GCs and analyzed by microarray. Gene expression differences between the five time points were assessed by ANOVA with a random factor accounting for the pairing of samples, and seven clusters of protein-coding genes representing distinct expression profiles were identified. These were used as input for subsequent bioinformatic analyses to identify enriched pathways and suggest upstream regulators. Subsets of genes were assessed to explore specific ovulatory functions. MAIN RESULTS AND THE ROLE OF CHANCE We identified 13 345 differentially expressed transcripts across the five time points (false discovery rate, <0.01) of which 58% were protein-coding genes. Two clusters of mainly downregulated genes represented cell cycle pathways and DNA repair. Upregulated genes showed one peak at 12 h that resembled the initiation of an inflammatory response, and one peak at 36 h that resembled the effector functions of inflammation such as vasodilation, angiogenesis, coagulation, chemotaxis and tissue remodelling. Genes involved in cell–matrix interactions as a part of cytoskeletal rearrangement and cell motility were also upregulated at 36 h. Predicted activated upstream regulators of ovulation included FSH, LH, transforming growth factor B1, tumour necrosis factor, nuclear factor kappa-light-chain-enhancer of activated B cells, coagulation factor 2, fibroblast growth factor 2, interleukin 1 and cortisol, among others. The results confirmed early regulation of several previously described factors in a cascade inducing meiotic resumption and suggested new factors involved in cumulus expansion and follicle rupture through co-regulation with previously described factors. LARGE SCALE DATA The microarray data were deposited to the Gene Expression Omnibus (www.ncbi.nlm.nih.gov/gds/, accession number: GSE133868). LIMITATIONS, REASONS FOR CAUTION The study included women undergoing ovarian stimulation and the findings may therefore differ from a natural cycle. However, the results confirm significant regulation of many well-established ovulatory genes from a series of previous studies such as amphiregulin, epiregulin, tumour necrosis factor alfa induced protein 6, tissue inhibitor of metallopeptidases 1 and plasminogen activator inhibitor 1, which support the relevance of the results. WIDER IMPLICATIONS OF THE FINDINGS The study increases our understanding of human ovarian function during ovulation, and the publicly available dataset is a valuable resource for future investigations. Suggested upstream regulators and highly differentially expressed genes may be potential pharmaceutical targets in fertility treatment and gynaecology. STUDY FUNDING/COMPETING INTEREST(S) The study was funded by EU Interreg ÔKS V through ReproUnion (www.reprounion.eu) and by a grant from the Region Zealand Research Foundation. None of the authors have any conflicts of interest to declare.

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