Molecular targets for the prevention and/or treatment of fibrosis, hypertrophic scars or keloids
The present invention relates to a therapeutic compound comprising: an agent that inhibits the activity of at least one gene selected from the group consisting of HIC1, FOXS1, CREB5, IRF7, POU2F2, STAT4, TCF4, and/or an agent that enhances the activity of at least one gene selected from the group consisting of MAF, MEOX2, SIX2.
1. A method for preventing and/or treating skin fibrosis, hypertrophic scar or keloid in a subject in need thereof, comprising administering to said skin fibrosis, hypertrophic scar, or keloid, or to tissue susceptible to developing skin fibrosis, hypertrophic scar, or keloid, a therapeutic compound comprising:
an agent that inhibits the expression of FOXS1, and/or an agent that inhibits the expression TCF4, and/or an agent that enhances the expression of MAF.
2. The method according to claim 1 further comprising: administering to the skin fibrosis, keloid, hypertrophic scar or tissue susceptible to developing skin fibrosis, hypertrophic scar, or keloid an agent that inhibits expression of SOX9.
3. The method according to claim 1 wherein the agent that inhibits expression of FOXS1 and/or the agent that enhances expression of MAF are selected from the group consisting of antisense DNA, antisense RNA, siRNA, shRNA, and ribozymes directed to FOXS1 RNA, optionally in the form of a plasmid or viral vector.
4. The method according to claim 1 wherein the agent that inhibits the expression of TGF4 and/or the agent that enhances the expression of MAF are selected from the group consisting of: anti-sense DNA, anti-sense RNA, siRNA shRNA, and ribozymes directed to TCF4 RNA, optionally in the form of plasmid and viral vectors.
5. The method according to claim 1 wherein the agent that enhances the expression of MAF is a cDNA encoding MAF, optionally in the form of a plasmid or viral vector.
6. The method according to claim 1 wherein it is for treating mammalian skin fibrosis, hypertrophic scars, or keloid, or tissue susceptible to developing skin fibrosis, hypertrophic scar, or keloid.
7. The method according to claim 1 wherein it is for treating human skin fibrosis, hypertrophic scars, keloid, or tissue susceptible to developing skin fibrosis, hypertrophic scar, or keloid.
8. The method according to claim 1 wherein the therapeutic compound is for topical application.
9. The method according to claim 1 wherein the therapeutic compound is for application to a dressing or impregnation of a dressing.
10. The method according to claim 1 further comprising administering to said skin fibrosis, hypertrophic scar, keloid, or tissue susceptible to developing skin fibrosis, hypertrophic scar or keloid at least one further therapeutic.
11. A method for treating a mammalian skin fibrosis, hypertrophic scar, keloid, or tissue susceptible to developing skin fibrosis, hypertrophic scar, or keloid, wherein said method comprises administering to said skin fibrosis, hypertrophic scar, keloid, or tissue susceptible to developing skin fibrosis, hypertrophic scar, or keloid a therapeutic compound comprising:
an agent that inhibits the expression of FOXS1, and/or an agent that inhibits the expression TCF4, and/or an agent that enhances the expression of MAF.
12. A method for treating a skin fibrosis, hypertrophic scar, keloid, or tissue susceptible to developing skin fibrosis, hypertrophic scar, or keloid, comprising administering to said skin fibrosis, hypertrophic scar, keloid, or skin tissue susceptible to developing fibrosis, hypertrophic scar, or keloid:
an agent that inhibits the expression of FOXS1, and/or an agent that inhibits the expression TCF4, and/or an agent that enhances the expression of MAF, wherein said agent modulates fibroblast and myofibroblast differentiation and/or activity.