Claims
- 1. A method of decreasing fibrosis in a tissue of a subject, comprising:
identifying a subject in need of decreased fibrosis; and administering to the subject an agent that inhibits a component of the VEGF signal transduction pathway, wherein the agent decreases a connective tissue growth factor (CTGF) activity in the tissue of the subject.
- 2. The method of claim 1, wherein the agent decreases the level or activity of VEGF or a VEGF receptor (VEGFR).
- 3. The method of claim 2, wherein the VEGFR is KDR, Flt1, Flt4 or neuropilin.
- 4. The method of claim 2, wherein the agent is selected from the group of: a VEGF binding or VEGF receptor (VEGFR) binding protein that inhibits VEGF binding to VEGFR; an antibody to VEGF or VEGFR that inhibits VEGF or VEGFR activity; a mutated VEGF or VEGFR or fragment thereof that inhibits VEGF signaling; a VEGF or VEGFR nucleic acid molecule that inhibits expression of VEGF or VEGFR; and a small molecule that inhibits transcription or activity of VEGF or VEGFR.
- 5. The method of claim 1, wherein the agent decreases the level or activity of AKT.
- 6. The method of claim 5, wherein the agent is selected from the group of: an AKT binding protein that inhibits AKT activity; an antibody to AKT that inhibits AKT activity; a mutated AKT or fragment thereof that inhibits AKT activity; an AKT nucleic acid molecule that inhibits expression of AKT; and a small molecule that inhibits transcription or activity of AKT.
- 7. The method of claim 1, wherein the agent decreases the level or activity of PI3 kinase.
- 8. The method of claim 7, wherein the agent is selected from the group of: a PI3 kinase binding protein that inhibits PI3 kinase activity; an antibody to PI3kinase that inhibits PI3 kinase activity; a mutated PI3 kinase or fragment thereof that inhibits PI3 kinase activity; a PI3 kinase nucleic acid molecule that inhibits expression of PI3 kinase; and a small molecule that inhibits transcription or activity of PI3 kinase.
- 9. The method of claim 7, wherein the agent is LY294002.
- 10. The method of claim 7, wherein the agent is wortmannin.
- 11. The method of claim 1, wherein the subject has a fibrosis related disorder.
- 12. The method of claim 1, wherein the tissue is skin tissue, lung tissue, cardiac tissue, kidney tissue, liver tissue, or retinal tissue.
- 13. A method of decreasing angiogenesis in a tissue of a subject, comprising:
identifying a subject in need of decreased angiogenesis; and administering to the subject an agent that inhibits a component of the VEGF signal transduction pathway, wherein the agent decreases a connective tissue growth factor (CTGF) activity in the tissue of the subject.
- 14. The method of claim 13, wherein the tissue is skin tissue, lung tissue, cardiac tissue, kidney tissue, liver tissue, retinal tissue, or cancerous or tumor tissue.
- 15. The method of claim 13, wherein the agent is selected from the group of:
a) an agent that inhibits VEGF activity; b) an agent that inhibits VEGFR signaling; c) an agent that inhibits PI3 kinase activity; d) an agent that inhibits a VEGFR interaction with p85 subunit of PI3-kinase; e) an agent that inhibits AKT activity; and f) an agent that inhibits ERK activity.
- 16. The method of claim 15, wherein the VEGFR is KDR or Flt1.
- 17. A method of increasing fibrosis in a subject, comprising:
identifying a subject in need of increased fibrosis; and administering to the subject an agent that induces a component of the VEGF signal transduction pathway, wherein the agent increases a connective tissue growth factor (CTGF) activity in the tissue of the subject.
- 18. The method of claim 17, wherein the agent is selected from the group of:
a) an agent that decreases a PKC activity; b) an agent that increases VEGF activity; c) an agent that increases VEGFR signaling; d) an agent that increases VEGFR interaction with p85 subunit of PI3 -kinase; e) an agent that increases PI3 kinase activity; and f) an agent that increases AKT activity.
- 19. The method of claim 17, wherein the agent is VEGF or placental growth factor (PlGF)
- 20. The method of claim 17, wherein the agent is a transition metal ion.
- 21. The method of claim 18, wherein the VEGFR is KDR or Flt1.
- 22. A method of screening for a compound that decreases fibrosis or angiogenesis, comprising:
providing a cell, tissue, or subject; contacting the cell, tissue, or subject with a test compound; and determining whether the test compound inhibits a component of the VEGF signaling pathway.
- 23. The method of claim 22, further comprising contacting the cell, tissue, or subject with VEGF.
- 24. The method of claim 22, further comprising assaying the cell, tissue or subject for a CTGF activity.
- 25. The method of claim 22, wherein the cell is an endothelial cell
- 26. The method of claim 22, wherein the cell is a bovine retinal endothelial cell (BREC) or bovine retinal pericyte (BRPC).
RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional application No. 60/219,244, filed on Jul. 18, 2000, the contents of which are incorporated herein by reference in their entirety.
FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] The U.S. Government may have certain rights in this invention pursuant to Grant No. EY5110 awarded by the National Institutes of Health to George L. King.
Provisional Applications (1)
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Number |
Date |
Country |
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60219244 |
Jul 2000 |
US |