KLF11 Protects against Venous Thrombosis via Suppressing Tissue Factor Expression

2021 ◽  
Author(s):  
Wenying Liang ◽  
Haocheng Lu ◽  
Jinjian Sun ◽  
Guizhen Zhao ◽  
Huilun Wang ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Tissue Factor ◽  
Gene Transcription ◽  
Loss Of Function ◽  
Expression Change ◽  
Causative Gene ◽  
Tnf Α ◽  
Gene Assay ◽  
Tf Gene

AbstractKrüppel-like factors (KLFs) play essential roles in multiple biological functions, including maintaining vascular homeostasis. KLF11, a causative gene for maturity-onset diabetes of the young type 7, inhibits endothelial activation and protects against stroke. However, the role of KLF11 in venous thrombosis remains to be explored. Utilizing stasis-induced murine deep vein thrombosis (DVT) model and cultured endothelial cells (ECs), we identified an increase of KLF11 expression under prothrombotic conditions both in vivo and in vitro. The expression change of thrombosis-related genes was determined by utilizing gain- and loss-of-function approaches to alter KLF11 expression in ECs. Among these genes, KLF11 significantly downregulated tumor necrosis factor-α (TNF-α)-induced tissue factor (TF) gene transcription. Using reporter gene assay, chromatin immunoprecipitation assay, and co-immunoprecipitation, we revealed that KLF11 could reduce TNF-α-induced binding of early growth response 1 (EGR1) to TF gene promoter in ECs. In addition, we demonstrated that conventional Klf11 knockout mice were more susceptible to developing stasis-induced DVT. These results suggest that under prothrombotic conditions, KLF11 downregulates TF gene transcription via inhibition of EGR1 in ECs. In conclusion, KLF11 protects against venous thrombosis, constituting a potential molecular target for treating thrombosis.

scholarly journals NMMHC IIA inhibition impedes tissue factor expression and venous thrombosis via Akt/GSK3β-NF-κB signalling pathways in the endothelium

2015 ◽  
Vol 114 (07) ◽  
pp. 173-185 ◽  
Author(s):  
Kefeng Zhai ◽  
Youmei Tang ◽  
Yuanyuan Zhang ◽  
Fang Li ◽  
Yan Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Tissue Factor ◽  
Nuclear Translocation ◽  
Thrombus Formation ◽  
Signalling Pathways ◽  
Dependent Manner ◽  
Tnf Α

SummaryNon-muscle myosin heavy chain IIA (NMMHC IIA) has been shown to be involved in thrombus formation and inflammatory microparticle release in endothelial cells. However, the role of NMMHC IIA in regulating the expression of tissue factor (TF) and deep venous thrombosis remains to be elucidated. In the present study, endothelial cells were stimulated with tumour necrosis factor-α (TNF-α) to induce TF expression. Pretreatment with the NMMHC II inhibitor blebbistatin suppressed the mRNA and protein expressions as well as the procoagulant activity of TF in a dose-dependent manner. Blebbistatin enhanced Akt and GSK3β phosphorylation and inhibited NF-κB p65 nuclear translocation and IκBα degradation. These observations were similar to the effect of CHIR99021, a GSK3β inhibitor. TF downregulation by blebbistatin was antagonised by the PI3K inhibitor, wortmannin. Furthermore, siRNA knockdown of NMMHC IIA but not IIB or IIC, inhibited TF expression, activated Akt/GSK3β and suppressed NF-κB signalling pathways, whereas the overexpression of NMMHC IIA increased TF expression. The binding of NMMHC IIA and TNF receptor 2 mediated signal internalisation in TNF-α-stimulated endothelial cells. Importantly, blebbistatin decreased endothelium NMMHC IIA and TF expression, deactivated GSK3β by inducing its phosphorylation, suppressed p65 nuclear translocation, and inhibited thrombus formation in a mouse deep venous thrombosis model. Our findings provide solid evidence that inhibition of NMMHC II most likely NMMHC IIA impedes TF expression and venous thrombosis via Akt/GSK3β-NF-κB signalling pathways in the endothelium both in vitro and in vivo. NMMHC IIA might be a potential novel target for the treatment of thrombotic disorders.

Abstract 805: Differential Regulation Of Cytokine-induced Alternative Splicing Of The TF Gene By Serine/Arginine Rich Protein Kinases

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Ursula Rauch ◽  
Andreas Eisenreich ◽  
Wolfgang Poller ◽  
Heinz-Peter Schultheiss
Keyword(s):  
Alternative Splicing ◽  
Protein Phosphorylation ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Splice Variant ◽  
Sr Protein ◽  
Phosphorylation State ◽  
Post Induction ◽  
Tnf Α ◽  
Tf Gene

Background: Higher eukaryotes control gene expression and increase protein diversity by alternative splicing of pre-mRNA. The Cdc2-like kinase (Clk) family, DNA topoisomerase I (DNA topo I) or Akt kinase are involved in splicing control by regulating the phosphorylation state of serine/arginine rich (SR) proteins. We recently showed that alternatively spliced human tissue factor (asHTF), a soluble isoform of tissue factor (TF), the primary initiator of coagulation, is expressed in HUVECs in response to inflammatory cytokines. This study investigated the role of Clks, DNA topo I and the PI3K-Pathway in regulation of TF-splicing in TNF-α induced HUVECs. Methods: HUVECs were incubated with inhibitors of Clks, DNA-topo I or PI3K and were then stimulated with TNF-α. The SR protein phosphorylation state was determined 2 min post induction. The full length (fl) TF and asHTF mRNA were assessed 60 min post induction by Real-Time PCR. Proteins were measured 5 and 8 hours after stimulation by Western blots and the cell thrombogenicity was analyzed via a chromogenic assay. Results: TNF-α inceased the mRNA expression of asHTF and flTF in HUVECs. The Clk-inhibitor completely inhibited the TNF-α induced expression of asHTF and reduced flTF by 30 %. Inhibition of DNA topo I increased asHTF expression and reduced the flTF expression. Inhibition of the PI3K/Akt-pathway had no effect on TF mRNA expression. Reduced Clk-inhibition the TF activity by 50 % whereas DNA topo I inhibition significantly decreased the procoagulant TF activity 8 hours post TNF-α induction. The Clk- and DNA-topo I-inhibitors altered the SR-protein phosphorylation pattern post TNF-α-induction. Additionally resulted inhibition of Clks in the generation of a third TF mRNA-splice variant, TF-A. Conclusion: Selective inhibition of Clks or DNA topo I leads to alterations of SR-protein phosphorylation and affects the differential expression of TF isoforms, thereby modulating the thrombogenicity of HUVECs. The inhibition of Clks contributes to the generation of a third TF splice variant. The inhibition of these kinases gives new insights into the regulation of the TF gene splicing process, which may result in new therapeutic strategies for modulating cellular thrombogenicity.

scholarly journals Retinoic Acid Selectively Inhibits Lipopolysaccharide Induction of Tissue Factor Gene Expression in Human Monocytes

Blood ◽  
1998 ◽  
Vol 91 (8) ◽  
pp. 2857-2865 ◽  
Author(s):  
Paul Oeth ◽  
Jin Yao ◽  
Sao-Tah Fan ◽  
Nigel Mackman
Keyword(s):  
Retinoic Acid ◽  
Tissue Factor ◽  
Human Monocytes ◽  
Monocytic Cells ◽  
All Trans Retinoic Acid ◽  
Tnf Α ◽  
Activated Monocytes ◽  
Tf Gene ◽  
Factor Α ◽  
Necrosis Factor

Expression of tissue factor (TF) by activated monocytes in several diseases leads to disseminated intravascular coagulation. Lipopolysaccharide (LPS)-induced monocyte TF expression is downregulated by the nuclear hormone all-trans retinoic acid (ATRA). In this study, we examined the mechanism by which ATRA inhibits monocyte TF expression. We show that ATRA selectively inhibited LPS induction of TF expression in human monocytes and monocytic THP-1 cells without affecting LPS induction of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8). Inhibition of TF expression occurred at the level of transcription as determined by nuclear run-on. ATRA did not significantly alter the binding or functional activity of the transcription factors c-Fos/c-Jun and c-Rel/p65, which are required for LPS induction of the TF promoter in monocytic cells. In contrast to the ATRA inhibition of the endogenous TF gene, LPS induction of the cloned TF promoter was not inhibited by ATRA in transiently transfected THP-1 cells. Our results demonstrate that ATRA selectively inhibited LPS-induced TF gene transcription in human monocytic cells by a mechanism that does not involve repression of AP-1– or NF-κB–mediated transcription.

Aging and obesity augment the stress-induced expression of tissue factor gene in the mouse

Blood ◽  
2002 ◽  
Vol 100 (12) ◽  
pp. 4011-4018 ◽  
Author(s):  
Koji Yamamoto ◽  
Takayoshi Shimokawa ◽  
Hong Yi ◽  
Ken-ichi Isobe ◽  
Tetsuhito Kojima ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Restraint Stress ◽  
Vascular Endothelial Cells ◽  
Obese Mice ◽  
Adipose Tissues ◽  
Aged Mice ◽  
Tnf Α ◽  
Underlying Mechanisms ◽  
Tf Gene ◽  
Factor Α

Hypercoagulability and thrombotic tendency are frequently induced by a variety of stressors. Clinically, aged subjects and obese patients are more susceptible to thrombotic diseases associated with stress, but the underlying mechanisms are unknown. We investigated the expression of a procoagulant gene, tissue factor (TF), in a mouse model of restraint stress. Twenty hours of restraint stress to mice caused a substantial induction of TF mRNA in several tissues. Importantly, the magnitude of induction of TF mRNA by restraint stress was larger in aged mice compared with young mice. In situ hybridization analysis of the stressed aged mice revealed that strong signals for TF mRNA were localized to renal epithelial cells, smooth muscle cells, adventitial cells, and adipocytes but not to vascular endothelial cells. These observations suggest that restraint stress induces the TF expression in a tissue-specific and cell type–specific manner. Genetically obese mice were also hyperresponsive to restraint stress in the induction of TF gene, especially in their livers and adipose tissues. Stress-induced microthrombi formation was pronounced in renal glomeruli and within the vasculature in adipose tissues of aged mice. Tumor necrosis factor-α (TNF-α) antigen in plasma was elevated by stress in aged mice and obese mice, and pretreatment of mice with anti–TNF-α antibody partially attenuated the stress-mediated induction of TF gene in adipose tissues in these mice. These results suggest that the induction of TF gene may increase the risk of stress-associated thrombosis in older and obese subjects and that TNF-α may be involved.

scholarly journals Role of tissue-factor bearing extracellular vesicles released from ovarian cancer cells in platelet aggregation in vitro and venous thrombosis in mice

2021 ◽  
Vol 2 ◽  
pp. 100020
Author(s):  
Tomoyuki Sasano ◽  
Min Soon Cho ◽  
Cristian Rodriguez-Aguayo ◽  
Emine Bayraktar ◽  
Mana Taki ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Platelet Aggregation ◽  
Venous Thrombosis ◽  
Cancer Cells ◽  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Ovarian Cancer Cells

Combining an in vitro reporter gene assay with metabolomics to identify tomato phytochemicals responsible for inducing electrophile-responsive element (EpRE)-mediated gene transcription

Metabolomics ◽  
2014 ◽  
Vol 11 (2) ◽  
pp. 302-311 ◽  
Author(s):  
Henriëtte D. L. M. van Eekelen ◽  
Linda Gijsbers ◽  
Chris A. Maliepaard ◽  
Robert A. M. Vreeburg ◽  
Richard Finkers ◽  
...  
Keyword(s):  
Reporter Gene ◽  
Gene Transcription ◽  
Reporter Gene Assay ◽  
Gene Assay ◽  
Responsive Element

scholarly journals Lipopolysaccharide induction of tissue factor gene expression in monocytic cells is mediated by binding of c-Rel/p65 heterodimers to a kappa B-like site.

1994 ◽  
Vol 14 (6) ◽  
pp. 3772-3781 ◽  
Author(s):  
P A Oeth ◽  
G C Parry ◽  
C Kunsch ◽  
P Nantermet ◽  
C A Rosen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tissue Factor ◽  
Binding Studies ◽  
Nf Kappa B ◽  
Monocytic Cells ◽  
Functional Studies ◽  
Nuclear Complex ◽  
Rapid Induction ◽  
Tf Gene

Exposure of monocytic cells to bacterial lipopolysaccharide (LPS) activates the NF-kappa B/Rel family of proteins and leads to the rapid induction of inflammatory gene products, including tissue factor (TF). TF is the primary cellular initiator of the coagulation protease cascades. Here we report the characterization of a nuclear complex from human monocytic cells that bound to a kappa B-like site, 5'-CGGAGTTTCC-3', in the 5'-flanking region of the human TF gene. This nuclear complex was activated by LPS with kinetics that preceded induction of the TF gene. In vitro binding studies demonstrated that the TF site bound translated c-Rel and p65 homodimers but not p50/p65 heterodimers or p50 homodimers. Base-pair substitutions in the TF site indicated that the presence of a cytosine at position 1 precluded binding of NF-kappa B. In fact, under low-ionic-strength conditions, the TF complex did not migrate with translated p50/p65 dimers but instead comigrated with c-Rel/p65 dimers. Antibodies against the NF-kappa B and Rel proteins and UV cross-linking studies revealed the presence of c-Rel and p65 and the absence of p50 in the TF complex and further showed that c-Rel/p65 heterodimers selectively bound to the TF kappa B-like site. Functional studies indicated that the TF site conferred LPS inducibility on a heterologous promoter and was transactivated by c-Rel or p65. Taken together, our results demonstrated that binding of c-Rel/p65 heterodimers to a novel kappa B-like site mediated LPS induction of TF gene expression in monocytic cells.

scholarly journals Identification of the ASPM-miR-26b-5p network associated with the aggressive traits of HCC cells

2020 ◽  
Author(s):  
Hong-Guang Li ◽  
Heng-Jun Gao ◽  
Fang-Feng Liu ◽  
Jun Liu
Keyword(s):  
Tumor Model ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Luciferase Reporter Gene ◽  
Luciferase Reporter Gene Assay ◽  
Gene Assay ◽  
Hcc Cells

Abstract Background: Even though earlier reports have revealed that abnormal spindle-like microcephaly associated (ASPM) exert essential roles in diverse malignancies, its relationship between specific microRNAs (miRNAs) in regulation of hepatocellular carcinoma (HCC) progression has never been elaborated. Methods: Bioinformatics analysis detected differentially expressed genes in HCC and normal. qRT-PCR was performed to detect expression of miR-26b-5p in HCC tissues and cells. HCC cells were transfected with plasmids and their proliferative ability and colony formation were detected with loss-of-function assay. The invasion of HCC cells was determined using Transwell assay. The expression of ASPM was detected by western blotting. Luciferase reporter gene assay was performed to detect the interaction between miR-26b-5p and ASPM. ASMP silencing cells were injected into mice to establish xenograft tumor model.Results: Herein, we proved that ASPM was upregulated in HCC and higher level of ASPM was significantly associated with worse survival in HCC patients. ASPM silencing restrained HCC cell proliferation, migration and invasion capacities in vitro. In vivo, downregulation of ASPM also suppressed HCC cells growth. Mechanistic analyses illustrated that ASPM was a directly target of miR-26b-5p. The expression of ASPM was negatively modulated by miR-26b-5p. Rescues assays displayed that miR-26b-5p inhibited HCC cells growth and invasion via modulating the expression of ASPM. Conclusions: Our work validated that miR-26b-5p restrained the aggressiveness of HCC cells through targeting ASPM.

scholarly journals Of numbers and movement – understanding transcription factor pathogenesis by advanced microscopy

2020 ◽  
Vol 13 (12) ◽  
pp. dmm046516
Author(s):  
Julia M. T. Auer ◽  
Jack J. Stoddart ◽  
Ioannis Christodoulou ◽  
Ana Lima ◽  
Kassiani Skouloudaki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Molecular Mechanisms ◽  
Gene Dosage ◽  
Super Resolution ◽  
Loss Of Function ◽  
Developmental Defects ◽  
Tf Gene

ABSTRACTTranscription factors (TFs) are life-sustaining and, therefore, the subject of intensive research. By regulating gene expression, TFs control a plethora of developmental and physiological processes, and their abnormal function commonly leads to various developmental defects and diseases in humans. Normal TF function often depends on gene dosage, which can be altered by copy-number variation or loss-of-function mutations. This explains why TF haploinsufficiency (HI) can lead to disease. Since aberrant TF numbers frequently result in pathogenic abnormalities of gene expression, quantitative analyses of TFs are a priority in the field. In vitro single-molecule methodologies have significantly aided the identification of links between TF gene dosage and transcriptional outcomes. Additionally, advances in quantitative microscopy have contributed mechanistic insights into normal and aberrant TF function. However, to understand TF biology, TF-chromatin interactions must be characterised in vivo, in a tissue-specific manner and in the context of both normal and altered TF numbers. Here, we summarise the advanced microscopy methodologies most frequently used to link TF abundance to function and dissect the molecular mechanisms underlying TF HIs. Increased application of advanced single-molecule and super-resolution microscopy modalities will improve our understanding of how TF HIs drive disease.

scholarly journals Αλληλεπίδραση μεταβιβαστών φλεγμονής και κυτταρικών πληθυσμών του αναπνευστικού επιθηλίου στην παθογένεια της ιδιοπαθούς πνευμονικής ίνωσης

2018 ◽  
Author(s):  
Ευάγγελος Μπούρος
Keyword(s):  
Real Time ◽  
Tissue Factor ◽  
Real Time Pcr ◽  
Dnase I ◽  
Rt Pcr ◽  
Tnf Α ◽  
Ifn Γ

Η Ιδιοπαθής Πνευμονική Ίνωση (IPF/ΙΠΙ) χαρακτηρίζεται από βλάβη του κυψελιδικού επιθηλίου, ρήξη της βασικής μεμβράνης και απορρύθμιση του επουλωτικού μηχανισμού με κυρίαρχο ρόλο να έχουν οι μυοϊνοβλάστες, κύτταρα αποκλειστικά υπεύθυνα για την υπερβολική παραγωγή και εναπόθεση κολλαγόνου στο πνευμονικό παρέγχυμα, που έχει ως αποτέλεσμα την αναδιαμόρφωσή του (remodeling). Αν και τα τελευταία χρόνια υπάρχει εντατική έρευνα σε ότι αφορά την κατανόηση των μηχανισμών που οδηγούν σε αυτή, παραμένουν πολλά ανεξερεύνητα μονοπάτια της παθογένεια της.Σκοπός της παρούσας μελέτης είναι η διερεύνηση του ρόλου των υποεπιθηλιακών μυοϊνοβλαστών του πνεύμονα (ΥΜΠ) και των διαλυτών μεσολαβητικών παραγόντων που επιδρούν στην ενεργοποίησή τους και την ανάπτυξη της ίνωσης σε ασθενείς με ιδιοπαθή πνευμονική ίνωση.Για το σκοπό της μελέτης ελήφθη βρογχοκυψελιδικό έκπλυμα (ΒΚΕ) χρησιμοποιώντας το εύκαμπτο βρογχοσκόπιο με την καθιερωμένη τεχνική από ασθενείς με γνωστή ΙΠΙ βάσει των ισχυόντων διαγνωστικών κριτηρίων (ATS/ERS/JRS/ALAT 2011). Για ομάδα ελέγχου χρησιμοποιήθηκε ΒΚΕ από ασθενείς με ιδιοπαθή μη ειδική διάμεση πνευμονία (iNSIP), πάθηση η οποία ανήκει μεν στις ιδιοπαθείς διάμεσες πνευμονίες, όμως είναι διακριτή ως προς την παθογένεια, την πορεία και θεραπεία της, καθώς και από φυσιολογικά άτομα τα οποία υποβλήθηκαν σε βρογχοσκόπηση για διαγνωστικούς λόγους. Οι ΥΜΠ απομονώθηκαν από χειρουργικά δείγματα υγιούς πνευμονικού ιστού τα οποία στη συνέχεια καλλιεργήθηκαν με προ-φλεγμονώδεις παράγοντες ή με ΒΚΕ από ασθενείς με IPF ή iNSIP και εκτιμήθηκε η ινωτική τους δράση με την δοκιμασία επούλωσης τραύματος, in vitro, με διαδοχική λήψη εικόνων μέσω ανάστροφου μικροσκοπίου Olympus, καθώς και με την παραγωγή κολλαγόνου (μg/mL). H απομόνωση του ολικού RNA έγινε με την χρήση του TRIzol και ο καθαρισμός του με τη χρήση του κιτ DNase I. Η έκφραση των ινωτικών παραγόντων Tissue factor (ΤF) και (TNF-like ligand 1A) TL1A από τους ΥΜΠ έγινε με real time PCR. Παράλληλα μελετήθηκε ο ρόλος των διαλυτών μεσολαβητών IL-1α, TNF-α και IFN-γ είτε μόνων είτε σε συνδυασμό, στην προαγωγή και έκφραση των ινωτικών παραγόντων, ιστικού παράγοντα (tissue factor, TF), TGF-β και TL1A από τους ΥΜΠ. Για την ποσοτικοποίησή τους χρησιμοποιήθηκε η τεχνική της RT-PCR μετά από σύνθεση του cDNA. O χαρακτηρισμός των μυοϊνοβλαστών και η εντόπιση του TL1A έγιναν με την τεχνική του ανοσοφθορισμού. Η έκφραση των ινωτικών παραγόντων TF και TL1A, καθώς και η παραγωγή κολλαγόνου από τους ΥΜΠ έγινε με RT-PCR και Sircol assay, αντιστοίχως. Από την παρούσα μελέτη προέκυψαν τα εξής αποτελέσματα. Διέγερση των ΥΜΠ με ΒΚΕ, ασθενών και μη (n=3), ή μαζί με τη προσθήκη συνδυασμού κυτταροκινών (IL-1α+TNF-α+IFN-γ) υπήρξε στατιστικά σημαντική αύξηση επιπέδου κολλαγόνου (IPF1: 183.99 μg/ml±14.03, p<0.01, IPF2: 118.50 μg/ml±5.04, p<0.05, IPF3: 126.23 μg/ml±2.7, p<0.05 και 3C: 184.72 μg/ml±29.72, p<0.05 σε σύγκριση με τα μη διεγερμένα: 63 μg/ml±1.2). Διέγερση των ΥΜΠ με ΒΚΕ, ασθενών και μη, ή μαζί με προ-φλεγμονώδεις κυτταροκίνες (IL-1α, TNF-α) έδειξε μια στατιστικά σημαντική αύξηση στη μεταγραφική ενεργότητα του TF (IPF: 3.56-fold±0.14, IL-1α: 2.5-fold±0.08, TNF-α: 2.3-fold±0.007, 2C: 2.7-fold±0.17, p<0.05 σε σύγκριση με τα μη διεγερμένα: 1.1-fold±0.3) και TL1A (IPF: 6.5-fold±0.8, IL-1α: 156-fold±14.94, TNF-α: 240-fold±7.8, 2C: 116-fold±3.6, p<0.01 σε σύγκριση με τα μη διεγερμένα: 1.3-fold±0.6). Τα επίπεδα του TL1A επιβεβαιώθηκαν με ανοσοφθορισμό. Είναι η πρώτη φορά που ο TL1A ερευνάται στους ΥΜΠ. Διέγερση των ΥΜΠ μαζί με προ-φλεγμονώδεις κυτταροκίνες δεν επέδειξε κάποια σημαντική αύξηση στη μεταναστευτική ικανότητα σε σύγκριση με αυτή που διεγέρθηκαν με ΒΚΕ (IPF2: 43.69%±2.16, p<0.01, IPF3: 36.49%±2.37, p<0.05).Συμπερασματικά, το BALF από ασθενείς με ΙΠΙ επάγει την ινωτική δραστηριότητα σε μυοϊνοβλάστες πνεύμονα, παρόμοιο με τους μεσολαβητές που σχετίζονται με την ίνωση του πνεύμονα, υποδεικνύοντας έναν βασικό ρόλο των ΥΜΠ στην ΙΠΙ. Η κυτταροκίνη TL1A είναι μία σημαντική ινωτική κυτταροκίνη, που εκλύεται αρκετά στις ινωτικές βλάβες και επιδρά στην ινωτική δραστηριότητα των μυοϊνοβλαστών των ασθενών με ΙΠΙ.

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