INT75484

Context Info Confidence 0.64 First Reported 1998 Last Reported 2010 Negated 0 Speculated 2 Reported most in Body Documents 21 Total Number 23 Disease Relevance 13.36 Pain Relevance 3.15

cell differentiation (Tgfbr1) signal transduction (Tgfbr1) cell motility (Tgfbr1) plasma membrane (Tgfbr1) embryo development (Tgfbr1) protein complex (Tgfbr1)

Anatomy Link Frequency chondrocytes 5 colon 1 Fibroblast 1 epithelial cells 1 mesenchymal cells 1 Tgfbr1 (Mus musculus)

Pain Link Frequency Relevance Heat Chronic pancreatitis 14 99.12 Osteoarthritis 1001 98.84 fibrosis 59 97.36 cytokine 60 95.52 Inflammation 37 5.00 metalloproteinase 35 5.00 Pain 11 5.00 Arthritis 11 5.00 anesthesia 6 5.00 ketamine 3 5.00

Disease Link Frequency Relevance Heat Targeted Disruption 26 100.00 Disease 161 99.38 Pancreatitis 14 99.12 Pancreatic Ductal Carcinoma 16 98.94 Osteoarthritis 1056 98.84 Cancer 256 98.28 Colon Cancer 21 98.24 Aging 191 97.76 Leukemia 15 97.44 Pulmonary Fibrosis 8 97.36

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In contrast to ALK5 signaling, TGF-?

Gene_expression (signaling) of ALK5

1) Confidence 0.64 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2659748 Disease Relevance 0.22 Pain Relevance 0

RI/ALK5 pathway and ALK5 inhibition prevents radiation-induced suppression of migration and sprouting

Gene_expression (pathway) of ALK5

2) Confidence 0.63 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2884035 Disease Relevance 0.11 Pain Relevance 0

1 in quiescent adult vasculature, ECs and mesenchymal cells were cocultured in Transwell or 3-D Matrigel in the presence of the ALK5 inhibitor SB-431542.

Gene_expression (presence) of ALK5 in mesenchymal cells

3) Confidence 0.57 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2659748 Disease Relevance 0.15 Pain Relevance 0

Radiation also induced expression of PAI-1 mRNA, an ALK5 target gene, which was inhibited by the small molecular ALK5 inhibitor SB431542 (Figure 8b).

Gene_expression (expression) of ALK5

4) Confidence 0.57 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2884035 Disease Relevance 0.09 Pain Relevance 0

Fibroblast cell lines from Tgfbr1 knock-in mouse

Gene_expression (knock) of Tgfbr1 in Fibroblast associated with targeted disruption

5) Confidence 0.42 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2888211 Disease Relevance 1.30 Pain Relevance 0.17

is reduced - and this is associated with a loss in ALK5 expression, and TGF?

Gene_expression (expression) of ALK5

6) Confidence 0.38 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.26 Pain Relevance 0.06

Blocking ALK5 expression using siRNA resulted in elevated expression of MMP-13 [85].

Gene_expression (expression) of ALK5

7) Confidence 0.38 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.30 Pain Relevance 0.08

Moreover, in two experimental models of OA - the DMM (meniscus destabilization) model and STR/ORT mice (spontaneous OA) - development of the disease was correlated with a loss of ALK5 expression.

Gene_expression (expression) of ALK5 associated with disease and osteoarthritis

8) Confidence 0.38 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.86 Pain Relevance 0.25

A prevailing expression of ALK5 will result in a dominance of the Smad2/3 signaling route, while ALK1 dominance will result in a stronger Smad1/5/8 pathway.

Gene_expression (expression) of ALK5

9) Confidence 0.38 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.56 Pain Relevance 0.17

on chondrocytes will be determined by the relative expression of ALK5 and ALK1.

Spec (determined) Gene_expression (expression) of ALK5 in chondrocytes

10) Confidence 0.38 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.50 Pain Relevance 0.14

We postulate that the loss of ALK5 expression and the concomitant elevated ratio of ALK1/ALK5 will have profound effects on chondrocyte behavior.

Gene_expression (expression) of ALK5 in chondrocyte

11) Confidence 0.38 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.73 Pain Relevance 0.22

As a result, the ratio of ALK1/ALK5 expressing cells strongly increased in OA articular chondrocytes.

Gene_expression (expressing) of ALK5 in chondrocytes associated with osteoarthritis

12) Confidence 0.38 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.87 Pain Relevance 0.26

In addition, overexpression of constitutive active ALK5 (Smad2/3) results in increased expression of aggrecan while constitutive ALK1 (Smad1/5/8) expression leads to elevated expression of MMP-13.

Gene_expression (overexpression) of ALK5

13) Confidence 0.33 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.26 Pain Relevance 0.06

In old animals, showing a decrease in the ALK5/ALK1 ratio, the protective effect of TGF?

Gene_expression (ratio) of ALK5

14) Confidence 0.33 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.63 Pain Relevance 0.19

The ALK1 (Smad1/5/8) and ALK5 (Smad3) signaling balance in chondrocytes apparently determines MMP-13 expression.

Gene_expression (/) of ALK5 in chondrocytes

15) Confidence 0.33 Published 2010 Journal Arthritis Res Ther Section Body Doc Link PMC2875624 Disease Relevance 0.26 Pain Relevance 0.06

In this study, the expression of TGFbeta1 and its receptors, TbetaRI and TbetaRII, is examined in 21 cases of PDC by immunohistochemistry using specific antibodies, and the results are compared with those for 13 cases of CP.

Gene_expression (expression) of TbetaRI associated with pancreatic ductal carcinoma and chronic pancreatitis

16) Confidence 0.33 Published 1998 Journal Pancreas Section Abstract Doc Link 9598806 Disease Relevance 1.11 Pain Relevance 0.61

In the epithelial cells of PDC and CP, there are no significant differences in the expression of TGFbeta1, TbetaRI, and TbetaRII.

Gene_expression (expression) of TbetaRI in epithelial cells associated with pancreatic ductal carcinoma and chronic pancreatitis

17) Confidence 0.33 Published 1998 Journal Pancreas Section Abstract Doc Link 9598806 Disease Relevance 1.15 Pain Relevance 0.66

Notably, signaling via ALK5 (Smad2/3 route) results in markedly different chondrocyte responses than ALK1 signaling (Smad1/5/8), and we postulate that the balance between ALK5 and ALK1 expression on chondrocytes will determine the overall effect of TGF?

Gene_expression (expression) of ALK5 in chondrocytes

18) Confidence 0.30 Published 2010 Journal Arthritis Res Ther Section Abstract Doc Link PMC2875624 Disease Relevance 0.52 Pain Relevance 0.22

with ALK5i or TGF-?

Gene_expression (with) of ALK5i

19) Confidence 0.23 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597201 Disease Relevance 0.32 Pain Relevance 0

receptors, which have been investigated most thoroughly, are ubiquitously expressed ALK-5 and endothel-specific ALK-1.

Gene_expression (expressed) of ALK-5

20) Confidence 0.12 Published 2010 Journal Journal of Oncology Section Body Doc Link PMC2871186 Disease Relevance 0.60 Pain Relevance 0

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