INT137135

Context Info Confidence 0.75 First Reported 2006 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 28 Total Number 29 Disease Relevance 11.55 Pain Relevance 2.45

extracellular space (THBS1) extracellular region (THBS1) cell adhesion (THBS1) structural molecule activity (THBS1)

Anatomy Link Frequency thyroid 1 cartilage 1 bone marrow 1 platelet 1 synapses 1 THBS1 (Homo sapiens)

Pain Link Frequency Relevance Heat Central nervous system 17 98.24 Arthritis 41 97.28 pain pelvic 30 96.48 cytokine 69 95.88 Inflammation 139 94.96 Gabapentin 14 93.52 agonist 58 91.60 Osteoarthritis 20 90.80 Kinase C 11 90.36 endometriosis 42 89.32

Disease Link Frequency Relevance Heat Pheochromocytoma 33 99.68 Endometriosis 64 99.44 Cancer 702 99.36 Wound Healing 30 99.20 Neuroblastoma 50 98.80 Synovitis 3 97.80 Experimental Arthritis 13 97.28 Leukemia 42 97.20 Osteoarthritis 48 97.08 Adhesions 17 96.64

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Anatomy

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Speculation

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Disease term

The platelet tests uniformly revealed rebound activation by all platelet measures (at least twofold increase) while being especially high for ADP-, and collagen-induced aggregation, platelet/endothelial cell adhesion molecule-1 (PECAM-1), glycoprotein (GP)Ib, GPIIb/IIIa activity, P-selectin, protease activated receptor (PAR)-1 thrombin receptor (activated and intact epitopes), and thrombospondin expression.

Gene_expression (expression) of thrombospondin in platelet associated with adhesions

1) Confidence 0.75 Published 2006 Journal Int. J. Clin. Pract. Section Abstract Doc Link 16846403 Disease Relevance 0.17 Pain Relevance 0.11

We next want to test whether E2F1 could up-regulate expression of the endogenous TSP1 gene.

Gene_expression (expression) of TSP1 gene

2) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

These observations suggested that the DNA binding activity of E2F1 is required for inducing TSP1 expression.

Gene_expression (expression) of TSP1

3) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

These observations suggested that E2F-1 could regulate TSP1 expression by directly binding to its promoter.

Gene_expression (expression) of TSP1

4) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

Using promoter assays, Northern blot and ChIP (chromatin immunoprecipitation) assays, we identified that E2F-1 could directly transactivate TSP1 expression by binding to its promoter, further expending TSP1's regulatory factors.

Gene_expression (expression) of TSP1

5) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0.21 Pain Relevance 0

Taking advantage of cell culture system and zebrafish model, we have identified that ELL could serve as a transcriptional factor to directly up-regulate TSP1 expression [31].

Gene_expression (expression) of TSP1

6) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0.80 Pain Relevance 0.17

Of cause, how E2F-1 acting its role in anti-angiogenesis through the regulation of TSP1 expression is definitely worth to be further investigated.

Gene_expression (expression) of TSP1

7) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0.48 Pain Relevance 0

In addition, we verified that the DNA binding domain and DNA binding ability of E2F-1 were required for transactivating TSP1 expression.

Gene_expression (expression) of TSP1

8) Confidence 0.72 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

Some authors, have been demonstrated that expresion of TSP-1 is higher in endometriotic lesions and is associated to the extent of their vascularization.

Gene_expression (expresion) of TSP-1 associated with endometriosis

9) Confidence 0.62 Published 2009 Journal J Ovarian Res Section Body Doc Link PMC2785805 Disease Relevance 1.34 Pain Relevance 0.51

All results of thrombospondin-1 expression were analysed by the Student's t-test.

Gene_expression (expression) of thrombospondin-1

10) Confidence 0.62 Published 2009 Journal J Ovarian Res Section Body Doc Link PMC2785805 Disease Relevance 0.44 Pain Relevance 0.22

To further verify E2F-1 binding sites in the promoter of TSP1, on the basis of TSP1-promoter (?

Gene_expression (basis) of TSP1

11) Confidence 0.62 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

Targeted overexpression of TSP1 in mice suppressed wound healing and tumorigenesis, while lack of functional TSP1 resulted in increased vascularization of selected tissues and significantly decreased the number of excitatory synapses [13], [21], [30].

Gene_expression (overexpression) of TSP1 in synapses associated with wound healing

12) Confidence 0.62 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0.90 Pain Relevance 0.24

In this study, through domain mapping for TSP1 promoter, we identified that the E2F-1 binding consensus sequence located in ?

Gene_expression (promoter) of TSP1

13) Confidence 0.62 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

At the same time, different function domains of E2F1 were cloned into Flag-tagged vector and co-transfected into 293 cells with TSP1 promoter luciferase reporter TSP1(?

Gene_expression (transfected) of TSP1

14) Confidence 0.62 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

Then, we did dose response experiments for E2F-1 overexpression on TSP1 promoter activity.

Gene_expression (overexpression) of TSP1

15) Confidence 0.62 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0.10 Pain Relevance 0

Flag empty vector or different dose of Flag-tagged E2F-1 expression vector, TSP1(?

Gene_expression (expression) of TSP1

16) Confidence 0.62 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0.09 Pain Relevance 0

At the same time, different function domains of E2F1 were cloned into Flag-tagged vector and co-transfected into 293 cells with TSP1 promoter luciferase reporter TSP1(?

Gene_expression (transfected) of TSP1

17) Confidence 0.62 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2955548 Disease Relevance 0 Pain Relevance 0

Thus, TSP1, CASP8, HIC1, DcR1, DcR2 and DR4 and RASSF1 were methylated frequently in both tumour types (Astuti et al. 2001c, Margetts et al. 2005).

Gene_expression (methylated) of TSP1 associated with cancer

18) Confidence 0.52 Published 2008 Journal Endocrine-Related Cancer Section Body Doc Link PMC2519165 Disease Relevance 1.51 Pain Relevance 0.06

Both PAR2 and PAR1 activation resulted in up-regulated expression of several genes (CD44, FOSL1, TNFRSF12A, RAB3A, COPEB, CORO1C, THBS1, SDC4) known to be important in cancer.

Gene_expression (expression) of THBS1 associated with cancer

19) Confidence 0.34 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2970545 Disease Relevance 0.45 Pain Relevance 0.21

Previously, it was known to be only activated by PAR1, but now we suggest that PAR2 can also trigger expression of thrombospondin-1.

Gene_expression (expression) of thrombospondin-1

20) Confidence 0.34 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2970545 Disease Relevance 0.75 Pain Relevance 0.04

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