title: Upregulation of hyaluronan and its binding receptors in an experimental model of chronic cyclosporine nephropathy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  These findings suggest that upregulation of HA and its binding receptors are involved in interstitial fibrosis in chronic CsA-induced renal injury.
authors.affiliation: Department of Internal Medicine, Kangnam Street Mary's Hospital, 505 Banpo-Dong, Seocho-Ku, Seoul 137-040, Korea.
authors.forename: Dong He
authors.initials: DH
authors.lastname: Han
authors.forename: Hyun Kuk
authors.initials: HK
authors.lastname: Song
authors.forename: So Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Song
authors.forename: Shang Guo
authors.initials: SG
authors.lastname: Piao
authors.forename: Hye Eun
authors.initials: HE
authors.lastname: Yoon
authors.forename: Jung Yeon
authors.initials: JY
authors.lastname: Ghee
authors.forename: Hyung Ju
authors.initials: HJ
authors.lastname: Yoon
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D016572:Cyclosporine; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D005355:Fibrosis; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000199:Actins; D016572:Cyclosporine; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D011956:Receptors, Cell Surface; C533408:Lyve1 protein, rat; C498862:Acta2 protein, rat