{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:38:02Z","timestamp":1790865482580,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2006,1,9]],"date-time":"2006-01-09T00:00:00Z","timestamp":1136764800000},"content-version":"vor","delay-in-days":253,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2005,5]]},"abstract":"<jats:p><jats:bold>A<jats:sc>bstract<\/jats:sc>: <\/jats:bold> Relaxin is well known for its actions on collagen remodeling. To improve our understanding of the physiologic role(s) of relaxin, the relaxin gene\u2010knockout (RLX\u2010KO) mouse was established by our group and subsequently phenotyped. Pregnant RLX\u2010KO mice underwent inadequate development of the pubic symphysis as well as the mammary glands and nipples compared to wild\u2010type mice, thus preventing lactation. Later studies showed that these deficiencies were associated with increased collagen, primarily in the nipple and vagina. Analysis of male RLX\u2010KO mice also demonstrated inadequate reproductive tract development. The testis, epididymis, and prostate of RLX\u2010KO mice showed delayed tissue maturation and growth associated with increased collagen deposition. In nonreproductive tissues, an age\u2010related increase in interstitial collagen (fibrosis) was also detected in the lung, heart, and kidneys of RLX\u2010KO mice and was associated with organ dysfunction. From 6\u20109 months of age and onwards, all organs of RLX\u2010KO mice, particularly male mice, underwent progressive increases in tissue weight and collagen content (all <jats:italic>P<\/jats:italic> &lt;.05) compared with wild\u2010type animals. The increased fibrosis contributed to bronchiole epithelium thickening and alveolar congestion (lung), atrial hypertrophy and increased ventricular chamber stiffness (heart) in addition to glomerulosclerosis (kidney). Treatment of RLX\u2010KO mice with recombinant human relaxin in early and developed stages of fibrosis caused the reversal of collagen deposition in the lung, heart, and kidneys. Together, these findings suggest that relaxin is a naturally occurring inhibitor of collagen deposition during normal development, aging, and pregnancy and can be used to prevent the progression of fibrosis.<\/jats:p>","DOI":"10.1196\/annals.1282.025","type":"journal-article","created":{"date-parts":[[2005,6,15]],"date-time":"2005-06-15T09:26:55Z","timestamp":1118827615000},"page":"173-181","source":"Crossref","is-referenced-by-count":84,"title":["The Relaxin Gene\u2010Knockout Mouse: A Model of Progressive Fibrosis"],"prefix":"10.1111","volume":"1041","author":[{"given":"CHRISHAN S.","family":"SAMUEL","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"CHONGXIN","family":"ZHAO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROSS A.D.","family":"BATHGATE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XIAO\u2010JUN","family":"DU","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ROGER J.","family":"SUMMERS","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"EDWARD P.","family":"AMENTO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LESLEY L.","family":"WALKER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARY","family":"MCBURNIE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LING","family":"ZHAO","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"GEOFFREY W.","family":"TREGEAR","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,1,9]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1958.02990040005002"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)87000-4"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119099"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.8.8295"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.1992.01880020047014"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12365206"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.49.4.577"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(03)00403-9"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.059003876.x"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000066302"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107882200"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.1.6404"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.2.687-696.2004"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod63.3.697"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2003-0013"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.LAB.0000079784.81186.B9"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0449fje"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00663-6"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0209"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00628.x"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2004.03.027"},{"key":"e_1_2_8_23_2","first-page":"F875","article-title":"Estradiol suppresses cell type I collagen synthesis via activation of the MAP kinase cascade","volume":"277","author":"Neugarten J.","year":"1999","journal-title":"Am. J. Physiol."},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00679.x"}],"container-title":["Annals of the New York Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1196%2Fannals.1282.025","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1196\/annals.1282.025","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T09:10:26Z","timestamp":1695633026000},"score":1,"resource":{"primary":{"URL":"https:\/\/nyaspubs.onlinelibrary.wiley.com\/doi\/10.1196\/annals.1282.025"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5]]},"references-count":23,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,5]]}},"alternative-id":["10.1196\/annals.1282.025"],"URL":"https:\/\/doi.org\/10.1196\/annals.1282.025","archive":["Portico"],"relation":{},"ISSN":["0077-8923","1749-6632"],"issn-type":[{"value":"0077-8923","type":"print"},{"value":"1749-6632","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5]]}}}