INT111037

Context Info Confidence 0.39 First Reported 2003 Last Reported 2008 Negated 1 Speculated 0 Reported most in Body Documents 5 Total Number 12 Disease Relevance 11.17 Pain Relevance 1.06

cytosol (Cdkn1b) cell death (Cdkn1b) nucleus (Cdkn1b) cell cycle (Cdkn1b) protein complex (Cdkn1b) response to stress (Cdkn1b)

Anatomy Link Frequency retina 6 blood 4 RG2 4 kidney 2 Cdkn1b (Rattus norvegicus)

Pain Link Frequency Relevance Heat cINOD 8 99.68 diclofenac 3 95.68 Kinase C 8 87.72 withdrawal 16 84.24 aspirin 3 65.44 Bile 3 61.60 antagonist 3 55.12 Central nervous system 32 51.04 Neuropeptide 8 26.96 Angina 9 5.00

Disease Link Frequency Relevance Heat Diabetes Mellitus 744 99.84 Congenital Anomalies 56 99.12 Hypertension 248 98.72 Apoptosis 130 98.56 Hyperglycemia 40 97.88 Retinal Diseases 24 97.68 Renal Disease 32 97.24 Hypertrophy 16 95.84 Albuminuria 8 93.64 Diabetic Retinopathy 112 84.84

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The induction of diabetes in SHR leads to a reduction in renal cell replication with concomitant overexpression of p27Kip1 [14]. p27Kip1-deficient mice do not develop the classic features of diabetic nephropathy such as renal hypertrophy, glomerular expression of fibronectin, and albuminuria, all of which are marked in wild-type mice [50].

Positive_regulation (overexpression) of Gene_expression (overexpression) of p27Kip1 associated with hypertrophy, diabetes mellitus, renal disease and albuminuria

1) Confidence 0.39 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2538494 Disease Relevance 1.42 Pain Relevance 0

These findings were associated with enhanced expression of p27Kip1 and with the classic abnormalities of diabetic retina—i.e., fibronectin accumulation, increased expression of retinal vascular endothelial growth factor (VEGF), and blood-retinal barrier breakdown.

Positive_regulation (enhanced) of Gene_expression (expression) of p27Kip1 in retina associated with diabetes mellitus and congenital anomalies

2) Confidence 0.39 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2538494 Disease Relevance 0.75 Pain Relevance 0.10

The increase in p27Kip1 expression in diabetic WKY, was not significant (0.9±0.5 and 1.6±0.5 positive score for normal and diabetic WKY; Figure 4C).

Positive_regulation (increase) of Gene_expression (expression) of p27Kip1 associated with diabetes mellitus

3) Confidence 0.39 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2538494 Disease Relevance 1.45 Pain Relevance 0

The ubiquitously expressed cyclin-dependent kinase (CDK) inhibitors, p21 and p27, were increased in all NSAID-treated cells.

Positive_regulation (increased) of Gene_expression (expressed) of p27 associated with cinod

4) Confidence 0.32 Published 2003 Journal J. Pharm. Pharmacol. Section Abstract Doc Link 12803774 Disease Relevance 0.13 Pain Relevance 0.76

This is the first demonstration of an association between increased expression of p27Kip1 and fibronectin accumulation in retinal tissue, and could contribute to thickening of the retinal capillary basement membrane seen in diabetic retina.

Positive_regulation (increased) of Gene_expression (expression) of p27Kip1 in retina associated with diabetes mellitus

5) Confidence 0.28 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2538494 Disease Relevance 1.11 Pain Relevance 0

The enhanced expression of p27Kip1 and fibronectin reflected a generalized response to hyperglycemia in target organs such as the kidney.

Positive_regulation (enhanced) of Gene_expression (expression) of p27Kip1 in kidney associated with hyperglycemia

6) Confidence 0.28 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2538494 Disease Relevance 1.12 Pain Relevance 0

This is the first demonstration of an association between increased expression of p27Kip1 and fibronectin accumulation in retinal tissue, and could contribute to thickening of the retinal capillary basement membrane seen in diabetic retina.

Positive_regulation (accumulation) of Gene_expression (expression) of p27Kip1 in retina associated with diabetes mellitus

7) Confidence 0.28 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2538494 Disease Relevance 1.07 Pain Relevance 0

Concomitant diabetes and hypertension attenuated the proliferation of retinal cells, and it is associated with an increase in p27Kip1 expression, fibronectin accumulation, and blood-retinal barrier breakdown.

Positive_regulation (increase) of Gene_expression (expression) of p27Kip1 in blood associated with diabetes mellitus and hypertension

8) Confidence 0.26 Published 2008 Journal Molecular Vision Section Abstract Doc Link PMC2538494 Disease Relevance 1.06 Pain Relevance 0

Additionally, diabetic hypertensive rats with a reduction in the number of BrdU-positive cells and enhanced p27Kip1 expression also displayed classic characteristics of early diabetic retinal disease: enhanced fibronectin and VEGF expression and greater blood-retinal barrier breakdown.

Positive_regulation (enhanced) of Gene_expression (expression) of p27Kip1 in blood associated with diabetes mellitus, hypertension and retinal diseases

9) Confidence 0.26 Published 2008 Journal Molecular Vision Section Body Doc Link PMC2538494 Disease Relevance 1.27 Pain Relevance 0.04

However, although RG2 cells were impaired for p53 and p16, p27 and procaspase 9 expression induced by BP were increased in these cells.

Positive_regulation (increased) of Gene_expression (expression) of p27 in RG2

10) Confidence 0.09 Published 2006 Journal Journal of Neurochemistry Section Body Doc Link PMC1804119 Disease Relevance 0.60 Pain Relevance 0.05

Thus, certain mechanisms of p53-independent activation of procaspase 9 and p27 induction may be involved in BP-induced cell apoptosis and cell growth inhibition.

Neg (independent) Positive_regulation (activation) of Gene_expression (induction) of p27 associated with apoptosis

11) Confidence 0.06 Published 2006 Journal Journal of Neurochemistry Section Body Doc Link PMC1804119 Disease Relevance 0.58 Pain Relevance 0.06

However, although RG2 cells were impaired for p53 and p16, p27 and procaspase 9 expression induced by BP were increased in these cells.

Positive_regulation (increased) of Gene_expression (expression) of p27 in RG2

12) Confidence 0.06 Published 2006 Journal Journal of Neurochemistry Section Body Doc Link PMC1804119 Disease Relevance 0.60 Pain Relevance 0.05

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