{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T20:16:51Z","timestamp":1774124211831,"version":"3.50.1"},"reference-count":35,"publisher":"The Endocrine Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,2,1]]},"abstract":"<jats:p>Relaxin is a naturally occurring regulator of collagen turnover. In this study, we determined the role of endogenous relaxin in the pathogenesis of primary tubulointerstitial fibrosis after unilateral ureteric obstruction (UUO). Four- to 6-wk-old relaxin (RLX) gene-knockout (RLX\u2212\/\u2212) and age-matched wild-type (RLX+\/+) mice, with equivalent baseline collagen levels, were subjected to UUO. Obstructed and contralateral kidneys were collected at d 0, 3, and 10 after surgery and analyzed for changes in inflammatory and fibrosis-related markers. UUO was associated with a progressive increase in fibrosis in all obstructed, but not contralateral kidneys. The increase in total collagen (hydroxyproline analysis) was associated with more \u03b1-smooth muscle actin (\u03b1-SMA) staining (myofibroblasts) and interstitial collagen sub-types (SDS-PAGE; types I, III, and V), whereas gelatin zymography demonstrated increased expression of matrix metalloproteinase-2 after surgery. By d 10 after UUO, there was a 5-fold decrease in RLX mRNA expression (quantitative RT-PCR) in RLX+\/+ animals. Total collagen and \u03b1-SMA expression were significantly greater in the obstructed kidneys of RLX\u2212\/\u2212 mice 3 d after UUO (both P &amp;lt; 0.05 vs. RLX+\/+ D3 after UUO), but comparable to that in RLX+\/+ animals 10 d after UUO. Administration of recombinant H2 relaxin to RLX\u2212\/\u2212 mice 4 d before UUO ameliorated the increase in collagen and \u03b1-SMA expression (both P &amp;lt; 0.05 vs. untreated RLX\u2212\/\u2212 mice) by d 3 after UUO. Expression of monocyte chemoattractant protein-1 and macrophage infiltration (inflammation) in addition to that of matrix metalloproteinases was unaffected by genotype after UUO. These combined data demonstrate that endogenous RLX acts as a modulating factor in tubulointerstitial fibrosis, a hallmark of progressive renal disease. This is likely to be via direct effects on renal myofibroblast function.<\/jats:p>","DOI":"10.1210\/en.2006-0814","type":"journal-article","created":{"date-parts":[[2006,11,10]],"date-time":"2006-11-10T01:48:38Z","timestamp":1163123318000},"page":"660-669","source":"Crossref","is-referenced-by-count":42,"title":["Endogenous Relaxin Is a Naturally Occurring Modulator of Experimental Renal Tubulointerstitial Fibrosis"],"prefix":"10.1210","volume":"148","author":[{"given":"Tim D.","family":"Hewitson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ishanee","family":"Mookerjee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary","family":"Masterson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chongxin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey W.","family":"Tregear","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gavin J.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chrishan S.","family":"Samuel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613494663100_R1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1053\/j.ackd.2005.07.011","article-title":"Progression in chronic kidney disease.","volume":"12","author":"Eddy","year":"2005","journal-title":"Adv Chronic Kidney Dis"},{"key":"2020071613494663100_R2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1097\/00041552-200003000-00006","article-title":"The role of tubulointerstitial injury in chronic renal failure.","volume":"9","author":"Becker","year":"2000","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2020071613494663100_R3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1159\/000168813","article-title":"Interstitial myofibroblasts in IgA glomerulonephritis.","volume":"15","author":"Hewitson","year":"1995","journal-title":"Am J Nephrol"},{"key":"2020071613494663100_R4","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/sj.ki.5000054","article-title":"Renal fibrosis: New insights into the pathogenesis and therapeutics.","volume":"69","author":"Liu","year":"2006","journal-title":"Kidney Int"},{"key":"2020071613494663100_R5","doi-asserted-by":"crossref","first-page":"F7","DOI":"10.1152\/ajprenal.00451.2003","article-title":"Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of action","volume":"287","author":"Liu","year":"2004","journal-title":"Am J Physiol Renal Physiol"},{"key":"2020071613494663100_R6","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/ndt\/gfh060","article-title":"Are there endogenous molecules that protect kidneys from injury? 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