Treatment of fibrosis-related disorders using fibronectin binding proteins and polypeptides
The present invention is directed to various uses of fibronectin binding proteins or polypeptides for treating and preventing fibrosis and fibrosis related conditions. The fibronectin binding proteins and polypeptides are also useful for treating conditions associated with vascular remodeling and cardiac dysfunction.
1. A method of improving heart function in a subject having an ischemic cardiac injury, said method comprising:
administering to the subject a peptide derived from a fibronectin binding bacterial adhesin protein, wherein the peptide binds fibronectin and inhibits deposition of fibronectin into the cardiac extracellular matrix to improve heart function in the subject.
2. The method according to claim 1 , wherein the peptide blocks fibronectin polymerization.
3. The method according to claim 1 , wherein the peptide blocks fibronectin-collagen binding.
4. A method of improving heart function in a subject having an ischemic cardiac injury, said method comprising:
administering to the subject a peptide derived from a fibronectin binding bacterial adhesin protein, wherein the peptide is selected from the group consisting of pUR 4 , FNZ r2 , and FNBPA 9-10 , and wherein the peptide binds fibronectin and inhibits deposition of fibronectin into the cardiac extracellular matrix to improve heart function in the subject.
5. The method according to claim 1 , wherein the subject has suffered or is suffering from a cardiac infarction and/or heart failure.
6. The method according to claim 4 , wherein the subject has suffered or is suffering from a cardiac infarction and/or heart failure.
7. The method according to claim 4 , wherein the peptide is pUR 4 .
8. A method of improving heart function in a subject having an ischemic cardiac injury, said method comprising:
administering to the subject a peptide comprising at least about 85 percent sequence identity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3, wherein the peptide binds fibronectin and inhibits deposition of fibronectin into the cardiac extracellular matrix to improve heart function in the subject.
9. The method according to claim 8 , wherein the subject has suffered or is suffering from a cardiac infarction and/or heart failure.
10. The method according to claim 8 , wherein the peptide comprises at least about 90 percent sequence identity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
11. The method according to claim 8 , wherein the peptide comprises at least about 95 percent sequence identity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
12. The method according to claim 8 , wherein the peptide is selected from the group consisting of the amino acids 6-101 of SEQ ID NO:2 or the amino acids 6-81 of SEQ ID NO:3.
13. A method of improving heart function in a subject having an ischemic cardiac injury, said method comprising:
administering to the subject a peptide consisting of the amino acid residues 13-61 of SEQ ID NO: 1, wherein the peptide binds fibronectin and inhibits deposition of fibronectin into the cardiac extracellular matrix to improve heart function in the subject.