Upregulation of hyaluronan and its binding receptors in an experimental model of chronic cyclosporine nephropathy.
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.
Han
Dong He
DH
Department of Internal Medicine, Kangnam Street Mary's Hospital, 505 Banpo-Dong, Seocho-Ku, Seoul 137-040, Korea.
Song
Hyun Kuk
HK
Lee
So Young
SY
Song
Ji-Hyun
JH
Piao
Shang Guo
SG
Yoon
Hye Eun
HE
Ghee
Jung Yeon
JY
Yoon
Hyung Ju
HJ
Kim
Jin
J
Yang
Chul Woo
CW
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
D000199:Actins; D016572:Cyclosporine; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid; D011956:Receptors, Cell Surface; C533408:Lyve1 protein, rat; C498862:Acta2 protein, rat