Lysyl oxidase-like 1 (LOXL1) and elastogenesis
Described are methods of treating and preventing conditions associated with a loss of elastic fibers. Also provided herein are methods of screening for agents useful in treating such conditions, and animal models of conditions associated with a loss of elastic fibers.
1. A method of treating a subject having pelvic organ prolapse or urinary incontinence, wherein the pelvic organ prolapse or urinary incontinence is associated with a loss of elastic fibers, the method comprising administering to the subject a therapeutically effective amount of a Lysyl Oxidase-Like-1 (LOXL1) polypeptide that is at least 95% identical to amino acids 26–574 of SEQ ID NO: 13 and can catalyze crosslinking of tropoelastin to form elastin.
2. The method of claim 1 , wherein the condition is pelvic organ prolapse.
3. The method of claim 1 , wherein the condition is urinary incontinence.
4. The method of claim 1 , wherein the LOXL1 polypeptide comprises SEQ ID NO:13.
5. The method of claim 1 , wherein the polypeptide comprises amino acids 26–574 of SEQ ID NO:13.
6. The method of claim 1 , wherein the subject is a human, and the LOXL1 polypeptide comprises amino acids 26–574 of SEQ ID NO:13.
7. The method of claim 1 , wherein the treatment results in an increase in elastin levels in a pelvic organ of the subject.
8. The method of claim 7 , wherein the pelvic organ is selected from the group consisting of bladder, uterus, vagina, rectum, urethra, vaginal wall, paraurethral connective tissues and pubourethral ligaments.
9. A method of preventing the development or progression of pelvic organ prolapse or urinary incontinence in a subject, wherein the subject has pelvic organ prolapse or urinary incontinence associated with a loss of elastic fibers, the method comprising administering to a subject a therapeutically effective amount of a Lysyl Oxidase-Like-1 (LOXL1) polypeptide that is at least 95% identical to amino acids 26–574 SEQ ID NO: 13 and can catalyze crosslinking of tropoelastin to form elastin.
10. The method of claim 9 , wherein the condition is pelvic organ prolapse.
11. The method of claim 9 , wherein the condition is urinary incontinence.
12. The method of claim 9 , wherein the LOXL1 polypeptide comprises SEQ ID NO:13.
13. The method of claim 9 , wherein the polypeptide comprises amino acids 26–574 of SEQ ID NO:13.
14. The method of claim 9 , wherein the treatment results in an increase in elastin levels in a pelvic organ of the subject.
15. The method of claim 14 , wherein the pelvic organ is selected from the group consisting of bladder, uterus, vagina, rectum, urethra, vaginal wall, paraurethral connective tissues and pubourethral ligaments.
16. The method of claim 9 , wherein the subject is a human, and the LOXL1 polypeptide comprises SEQ ID NO:13.
17. A method of treating a subject having pelvic organ prolapse or urinary incontinence, wherein the pelvic organ prolapse or urinary incontinence is associated with a loss of elastic fibers, the method comprising administering to the subject a therapeutically effective amount of a Lysyl Oxidase-Like-1 (LOXL1) polypeptide that is at least 95% identical to amino acids 26-607 of SEQ ID NO: 14 and can catalyze crosslinking of tropoelastin to form elastin.
18. The method of claim 17 , wherein the polypeptide comprises amino acids 26-607 of SEQ IDNO:14.
19. The method of claim 17 , wherein the polypeptide comprises SEQ ID NO: 14.
20. A method of treating a subject having pelvic organ prolapse or urinary incontinence, wherein the pelvic organ prolapse or urinary incontinence is associated with a loss of elastic fibers, the method comprising administering to the subject a therapeutically effective amount of a Lysyl Oxidase-Like-l (LOXL1) polypeptide that is at least 95% identical to SEQ ID NO: 15 and can catalyze crosslinking of tropoelastin to form elastin.
21. The method of claim 20 , wherein the polypeptide comprises SEQ ID NO: 15.
22. A method of treating a subject having pelvic organ prolapse or urinary incontinence, wherein the pelvic organ prolapse or urinary incontinence is associated with a loss of elastic fibers, the method comprising administering to the subject a therapeutically effective amount of a Lysyl Oxidase-Like-1 (LOXL1) polypeptide that is at least 95% identical to SEQ ID NO: 16 and can catalyze crosslinking of tropoelastin to form elastin.
23. The method of claim 22 , wherein the polypeptide comprises SEQ ID NO: 16.
24. A method of preventing the development or progression of pelvic organ prolapse or urinary incontinence in a subject, wherein the subject has pelvic organ prolapse or urinary incontinence associated with a loss of elastic fibers, the method comprising administering to a subject a therapeutically effective amount of a Lysyl Oxidase-Like-1 (LOXL1) polypeptide that is at least 95% identical to amino acids 26-607 of SEQ ID NO:14 and can catalyze crosslinking of tropoelastin to form elastin.
25. The method of claim 24 , wherein the polypeptide comprises amino acids 26-607 of SEQ ID NO:14.
26. The method of claim 24 , wherein the polypeptide comprises SEQ ID NO:14.
27. A method of preventing the development or progression of pelvic organ prolapse or urinary incontinence in a subject, wherein the subject has pelvic organ prolapse or urinary incontinence associated with a loss of elastic fibers, the method comprising administering to a subject a therapeutically effective amount of a Lysyl Oxidase-Like-1 (LOXL1) polypeptide that is at least 95% identical to SEQ ID NO: 15 and can catalyze crosslinking of tropoelastin to form elastin.
28. The method of claim 27 , wherein the polypeptide comprises SEQ ID NO:15.
29. A method of preventing the development or progression of pelvic organ prolapse or urinary incontinence in a subject, wherein the subject has pelvic organ prolapse or urinary incontinence associated with a loss of elastic fibers, the method comprising administering to a subject a therapeutically effective amount of a Lysyl Oxidase-Like-1 (LOXL1) polypeptide that is at least 95% identical to SEQ ID NO: 16 and can catalyze crosslinking of tropoelastin to form elastin.
30. The method of claim 29 , wherein the polypeptide comprises SEQ ID NO:16.