Dong He Han, Hyun Kuk Song, So Young Lee, Ji-Hyun Song, Shang Guo Piao, Hye Eun Yoon, Jung Yeon Ghee, Hyung Ju Yoon, Jin Kim, Chul Woo Yang
{"title":"Upregulation of hyaluronan and its binding receptors in an experimental model of chronic cyclosporine nephropathy.","authors":"Dong He Han, Hyun Kuk Song, So Young Lee, Ji-Hyun Song, Shang Guo Piao, Hye Eun Yoon, Jung Yeon Ghee, Hyung Ju Yoon, Jin Kim, Chul Woo Yang","doi":"10.1111/j.1440-1797.2009.01167.x","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>Hyaluronan (HA) is an important extracellular matrix (ECM) proteoglycan. The localization of HA and its binding receptors, CD44 and LYVE-1, was evaluated in an experimental model of chronic cyclosporine A (CsA)-induced nephropathy.</p><p><strong>Methods: </strong>Sprague-Dawley rats maintained on a low-salt diet (0.05% sodium) received an s.c. injection of vehicle (1 mL/kg per day olive oil; VH groups) or CsA (15 mg/kg per day; CsA groups) for 1 or 4 weeks. Induction of chronic CsA nephropathy was evaluated according to renal function and pathology and expression of HA, CD44, LYVE-1, ED-1 and alpha-smooth muscle actin (alpha-SMA).</p><p><strong>Results: </strong>CsA treatment for 4 weeks caused renal dysfunction, which was accompanied by typical striped interstitial fibrosis. In the VHroup, HA immunoreactivity was observed only in the inner medulla. However, the area of HA immunoreactivity increased with the duration of CsA treatment: CsA treatment for 1 week extended HA immunoreactivity to the outer medulla, and CsA treatment for 4 weeks caused a further extension of HA immunoreactivity to the cortex, which was vulnerable to CsA-induced renal injury. HA binding receptor, CD44 and LYVE-1 expression were also upregulated in the CsA groups, and were localized to the area of fibrosis and the peritubular capillaries of the cortex. In the CsA groups, ED-1 and alpha-SMA were predominantly expressed in fibrotic areas in which HA had accumulated.</p><p><strong>Conclusion: </strong>These findings suggest that upregulation of HA and its binding receptors are involved in interstitial fibrosis in chronic CsA-induced renal injury.</p>","PeriodicalId":520716,"journal":{"name":"Nephrology (Carlton, Vic.)","volume":" ","pages":"216-24"},"PeriodicalIF":0.0000,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1440-1797.2009.01167.x","citationCount":"18","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nephrology (Carlton, Vic.)","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/j.1440-1797.2009.01167.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 18
Abstract
Aim: Hyaluronan (HA) is an important extracellular matrix (ECM) proteoglycan. The localization of HA and its binding receptors, CD44 and LYVE-1, was evaluated in an experimental model of chronic cyclosporine A (CsA)-induced nephropathy.
Methods: Sprague-Dawley rats maintained on a low-salt diet (0.05% sodium) received an s.c. injection of vehicle (1 mL/kg per day olive oil; VH groups) or CsA (15 mg/kg per day; CsA groups) for 1 or 4 weeks. Induction of chronic CsA nephropathy was evaluated according to renal function and pathology and expression of HA, CD44, LYVE-1, ED-1 and alpha-smooth muscle actin (alpha-SMA).
Results: CsA treatment for 4 weeks caused renal dysfunction, which was accompanied by typical striped interstitial fibrosis. In the VHroup, HA immunoreactivity was observed only in the inner medulla. However, the area of HA immunoreactivity increased with the duration of CsA treatment: CsA treatment for 1 week extended HA immunoreactivity to the outer medulla, and CsA treatment for 4 weeks caused a further extension of HA immunoreactivity to the cortex, which was vulnerable to CsA-induced renal injury. HA binding receptor, CD44 and LYVE-1 expression were also upregulated in the CsA groups, and were localized to the area of fibrosis and the peritubular capillaries of the cortex. In the CsA groups, ED-1 and alpha-SMA were predominantly expressed in fibrotic areas in which HA had accumulated.
Conclusion: These findings suggest that upregulation of HA and its binding receptors are involved in interstitial fibrosis in chronic CsA-induced renal injury.