Methods of modulating apoptosis by administration of relaxin agonists or antagonists

Abstract

The present invention relates to the discovery that relaxin is associated with the development or maturation of body tissues. Knockouts of the gene encoding relaxin result in various abnormalities in the development of various tissues. The present invention provides methods of modulating apoptosis by administering a relaxin agonist or antagonist to a subject.

1 . A method of modulating apoptosis, comprising: 
 administering to a subject in need thereof an effective amount of a relaxin agonist for a period of time sufficient to decrease apoptosis in cells expressing a relaxin receptor.    
     
     
         2 . The method of  claim 1 , wherein the cells are from the liver, kidney, spleen, thymus, brain, heart, intestine, skin, lung, the male reproductive tract, or the female reproductive tract.  
     
     
         3 . The method of  claim 2 , wherein the male reproductive tract tissue is prostate, epididymis, seminal vesicles or testes.  
     
     
         4 . The method of  claim 2 , wherein the female reproductive tract tissue is uterus, cervix, the interpubic ligament, or connective tissues within the pelvic girdle.  
     
     
         5 . The method of  claim 2 , wherein the number of apoptotic cells decreases.  
     
     
         6 . The method of  claim 1 , wherein tissue maturation is stimulated.  
     
     
         7 . The method of  claim 6 , wherein fibrosis is reduced.  
     
     
         8 . The method of  claim 6 , wherein the tissue is male reproductive tract tissue.  
     
     
         9 . The method of  claim 8 , wherein the tissue is prostatic tissue, epididymal tissue, seminiferous tissue, testicular tissue or sperm.  
     
     
         10 . The method of  claim 9 , wherein the tissue is testicular tissue.  
     
     
         11 . The method of  claim 10 , wherein the maturation is an increase in cell number in an under-developed testes.  
     
     
         12 . The method of  claim 9 , wherein the number of viable sperm cells increases.  
     
     
         13 . The method of  claim 1 , wherein the subject has a relaxin-deficient condition.  
     
     
         14 . The method of  claim 13 , wherein the relaxin-deficient condition is immature tissue, excessive collagen deposition, or low sperm count.  
     
     
         15 . The method of  claim 14 , wherein the immature tissue is immature male productive tract tissue.  
     
     
         16 . The method of  claim 15 , wherein the immature male reproductive tract tissue is underdeveloped testes.  
     
     
         17 . The method of  claim 1 , wherein excessive collagen deposition is reduced.  
     
     
         18 . The method of  claim 1 , wherein the relaxin agonist is relaxin, a relaxin analog, a small molecule relaxin effector, or a relaxin nucleic acid.  
     
     
         19 . The method of  claim 18 , wherein the relaxin is vertebrate relaxin.  
     
     
         20 . The method of  claim 19 , wherein the relaxin is human relaxin.  
     
     
         21 . The method of  claim 1 , wherein the administering is by infusion, injection, oral delivery, nasal delivery, intrapulmonary delivery, rectal delivery, transdermal delivery, interstitial delivery or subcutaneous delivery.  
     
     
         22 . The method of  claim 21 , wherein the administering is by delayed release delivery.  
     
     
         23 . The method of  claim 21 , wherein the subcutaneous delivery is by infusion or injection.  
     
     
         24 . The method of  claim 21 , wherein the administering is by intrapulmonary, subcutaneous or transdermal delivery.  
     
     
         25 . The method of  claim 1 , wherein the administering comprises delivery of a vector encoding the relaxin agonist.  
     
     
         26 . The method of  claim 1 , wherein the vector is an expression vector, and whereby the relaxin agonist is expressed in the cells.  
     
     
         27 . The method of  claim 1 , wherein the administering comprises delivery of a relaxin or relaxin analog nucleic acid.  
     
     
         28 . The method of  claim 1 , wherein the subject is a post-pubescent subject.  
     
     
         29 . The method of  claim 1 , wherein the subject is a pre-pubescent subject.  
     
     
         30 . A method of modulating apoptosis in a population of cells expressing a relaxin receptor, comprising: 
 administering to a subject in need thereof an effective amount of an antagonist of relaxin for a period of time sufficient to increase apoptosis in the cell population expressing the relaxin receptor.    
     
     
         31 . The method of  claim 30 , wherein the relaxin antagonist inhibits binding of relaxin to relaxin receptor.  
     
     
         32 . The method of  claim 30 , wherein the relaxin antagonist reduces relaxin-associated tissue remodeling.  
     
     
         33 . The method of  claim 30 , wherein the cell population is from heart, brain, liver, kidney, spleen, thymus, skin, female reproductive tract tissue or male reproductive tract tissue.  
     
     
         34 . The method of  claim 33 , wherein the male reproductive tract tissue is prostate, epididymis, seminal vesicles or testes.  
     
     
         35 . The method of  claim 34 , wherein the tissue is prostatic tissue.  
     
     
         36 . The method of  claim 33 , wherein the male reproductive tract tissue is mature.  
     
     
         37 . The method of  claim 33 , wherein the tissues of the female reproductive tract are the uterus, cervix, the interpubic ligament, and connective tissues within the pelvic girdle.  
     
     
         38 . The method of  claim 30 , wherein the cell population comprises fibroblasts, osteoblasts, monocytes, epithelial cells or endothelial cells.  
     
     
         39 . The method of  claim 30 , wherein the relaxin antagonist is a relaxin binding agent, a relaxin receptor binding agent, or a relaxin antisense nucleic acid.  
     
     
         40 . The method of  claim 39 , wherein the relaxin binding agent is an anti-relaxin antibody, a soluble relaxin receptor, or a small molecule relaxin antagonist.  
     
     
         41 . The method of  claim 40 , wherein the antibody is a monoclonal antibody, a polyclonal antibody, a single chain antibody, an Fab, Fab′, an F(ab′) 2 , an Fv, a single heavy chain, or a chimeric antibody.  
     
     
         42 . The method of  claim 39 , wherein the relaxin receptor binding agent is an anti-relaxin receptor antibody, a relaxin analog, or a small molecule relaxin receptor antagonist.  
     
     
         43 . The method of  claim 42 , wherein the antibody is a monoclonal antibody, a polyclonal antibody, a single chain antibody, an Fab, Fab′, an F(ab′) 2 , an Fv, a single heavy chain, or a chimeric antibody.  
     
     
         44 . The method of  claim 30 , wherein the administering is by infusion, injection, oral delivery, nasal delivery, intrapulmonary delivery, rectal delivery, transdermal delivery, interstitial delivery, or subcutaneous delivery.  
     
     
         45 . The method of  claim 44 , wherein the administering is by delayed release delivery.  
     
     
         46 . The method of  claim 44 , wherein the subcutaneous delivery is by infusion or injection.  
     
     
         47 . The method of  claim 44 , wherein the administering is by intrapulmonary, subcutaneous or transdermal delivery.  
     
     
         48 . The method of  claim 30 , wherein the administering comprises delivery of a vector encoding the relaxin antagonist.  
     
     
         49 . The method of  claim 30 , wherein the vector is an expression vector, and whereby the relaxin antagonist is expressed in the cell population.  
     
     
         50 . The method of  claim 30 , wherein the administering comprises delivery of a relaxin or relaxin receptor antisense nucleic acid.  
     
     
         51 . The method of  claim 30 , wherein increased apoptosis reduces unwanted cell accumulation.  
     
     
         52 . The method of  claim 51 , wherein the unwanted cells accumulation is hyperplasia, hypertrophy, cancer or neoplasia.