Compositions, methods and kits relating to REMODELIN
OwnerVolkhard Lindner, Robert E. Frieselinventors
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OwnerVolkhard Lindner, Robert E. Frieselinventors
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The invention relates to novel nucleic acids encoding a mammalian adventitia inducible and bone expressed gene designated REMODEL, and proteins encoded thereby, whose expression is increased in certain diseases, disorders, or conditions, including, but not limited to, negative remodeling, arterial restenosis, vessel injury, ectopic ossification, fibrosis, and the like. REMODELIN also plays a role in cell-cell and cell-matrix adhesion, bone density, bone formation, dorsal closure, bone mineralization, calcification/ossification, and is associated with spina bifida-like phenotype. In addition, the invention relates to affecting REMODELIN expression by administration of TGF-β and control of cellular gene expression using REMODELIN. The invention further relates to methods of treating and detecting these diseases, disorders or conditions, comprising modulating or detecting REMODELIN expression and/or production of REMODELIN polypeptide.
An isolated nucleic acid encoding a mammalian REMODELIN, or a fragment thereof.
An isolated nucleic acid encoding a mammalian REMODELIN, wherein the amino acid sequence of said REMODELIN shares at least about 6% sequence identity with an amino acid sequence of at least one of SEQ ID NO:
An isolated polypeptide comprising a mammalian REMODELIN.
An antibody that specifically binds with a mammalian REMODELIN molecule polypeptide, or a fragment thereof.
A method of diagnosing arterial restenosis in a mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of REMODELIN in said biological sample, and comparing the level of REMODELIN in said biological sample with the level of REMODELIN in a biological sample obtained from a like mammal not afflicted with arterial restenosis, wherein a higher level of REMODELIN in said biological sample from said mammal compared with the level of REMODELIN in said biological sample from said like mammal is an indication that said mammal is afflicted with arterial restenosis, thereby diagnosing arterial restenosis in said mammal.
A method of diagnosing negative remodeling in a mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of REMODELIN in said biological sample, and comparing the level of REMODELIN in said biological sample with the level of REMODELIN in a biological sample obtained from a like mammal not afflicted with negative remodeling, wherein a higher level of REMODELIN in said biological sample from said mammal compared with the level of REMODELIN in said biological sample from said like mammal is an indication that said mammal is afflicted with negative remodeling, thereby diagnosing negative remodeling in said mammal.
A method of diagnosing fibrosis in a mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of REMODELIN in said biological sample, and comparing the level of REMODELIN in said biological sample with the level of REMODELIN in a biological sample obtained from a like mammal not afflicted with fibrosis, wherein a higher level of REMODELIN in said biological sample from said mammal compared with the level of REMODELIN in said biological sample from said like mammal is an indication that said mammal is afflicted with fibrosis, thereby diagnosing fibrosis in said mammal.
A method of identifying a compound that affects expression of REMODELIN in a cell, said method comprising contacting a cell with a test compound and comparing the level of REMODELIN expression in said cell with the level of REMODELIN expression in an otherwise identical cell not contacted with said test compound, wherein a higher or lower level of REMODELIN expression in said cell contacted with said test compound compared with the level of REMODELIN expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound affects expression of REMODELIN in a cell.
A method of identifying a compound that reduces expression of REMODELIN in a cell, said method comprising contacting a cell with a test compound and comparing the level of REMODELIN expression in said cell with the level of REMODELIN expression in an otherwise identical cell not contacted with said test compound, wherein a lower level of REMODELIN expression in said cell contacted with said test compound compared with the level of REMODELIN expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound reduces expression of REMODELIN in a cell.
A method of identifying a compound that affects TGF-β signaling, said method comprising contacting a cell with a test compound and comparing the level of REMODELIN expression in said cell with the level of REMODELIN expression in an otherwise identical cell not contacted with said test compound, wherein a higher or lower level of REMODELIN expression in said cell contacted with said test compound compared with the level of REMODELIN expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound affects TGF-β signaling in a cell.
A kit for treating a bone disease in a mammal, said kit comprising a REMODELIN expression-inhibiting amount of an inhibitor of REMODELIN expression, said kit further comprising an applicator, and an instructional material for the use thereof.
A kit for treating a cartilage disease in a mammal, said kit comprising a REMODELIN expression-inhibiting amount of an inhibitor of REMODELIN expression, said kit further comprising an applicator, and an instructional material for the use thereof.
A kit for inhibiting tissue calcification, said kit comprising a REMODELIN expression-inhibiting amount of an inhibitor of REMODELIN expression, said kit further comprising an applicator, and an instructional material for the use thereof.
A method of increasing REMODELIN expression in a mammal, said method comprising administering a REMODELIN expression increasing amount of TGF-β to said mammal, thereby increasing REMODELIN expression in said mammal.
A method of reducing REMODELIN expression in a mammal, said method comprising administering a REMODELIN expression reducing amount of TGF-β receptor type II to said mammal, thereby inhibiting signaling via TGF-β receptor type II and reducing expression of REMODELIN in said mammal.
A method of affecting cellular gene expression in a mammal, said method comprising administering a nucleic acid encoding REMODELIN to said mammal, thereby affecting cellular gene expression in said mammal.
A method of affecting cellular gene expression in a mammal, said method comprising administering a nucleic acid antisense to a nucleic acid encoding REMODELIN to said mammal, thereby affecting cellular gene expression in said mammal.
A method of treating bone disease in a mammal in need of such treatment, said method comprising administering to a mammal afflicted with said bone disease a REMODELIN expression-inhibiting amount of an inhibitor of REMODELIN expression, thereby inhibiting REMODELIN expression and treating said bone disease in said mammal.
A method of treating cartilage disease in a mammal in need of such treatment, said method comprising administering to a mammal afflicted with said cartilage disease a REMODELIN expression-inhibiting amount of an inhibitor of REMODELIN expression, thereby inhibiting REMODELIN expression and treating said cartilage disease in said mammal.
A method of diagnosing a bone disease in a mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of REMODELIN in said biological sample, and comparing the level of REMODELIN in said biological sample with the level of REMODELIN in a biological sample obtained from an otherwise identical mammal not afflicted with bone disease, wherein a higher level of REMODELIN in said biological sample from said mammal compared with said level of REMODELIN in said biological sample from said like mammal is an indication that said mammal is afflicted with bone disease, thereby diagnosing said bone disease in said mammal.
A method of diagnosing a collagen disease in a mammal, said method comprising obtaining a biological sample from said mammal, assessing the level of REMODELIN in said biological sample, and comparing the level of REMODELIN in said biological sample with the level of REMODELIN in a biological sample obtained from an otherwise identical mammal not afflicted with a collagen disease, wherein a higher level of REMODELIN in said biological sample from said mammal compared with said level of REMODELIN in said biological sample from said like mammal is an indication that said mammal is afflicted with a collagen disease, thereby diagnosing said collagen disease in said mammal.
Dependencies are inferred from the claim text.