Matrix accumulation in mesangial cells exposed to cyclosporine a requires a permissive genetic background

被引:20
作者
Fornoni, A [1 ]
Lenz, O [1 ]
Tack, I [1 ]
Potier, M [1 ]
Elliot, SJ [1 ]
Striker, LJ [1 ]
Striker, GE [1 ]
机构
[1] Univ Miami, Sch Med, Div Nephrol, Renal Cell Biol Lab, Miami, FL 33101 USA
关键词
D O I
10.1097/00007890-200008270-00009
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Chronic nephrotoxicity is an important adverse effect of cyclosporine A (CsA) therapy. Tubulo-interstitial lesions and arteriolopathy are common histologic findings. Glomerular lesions are also described, but they are of variable severity. The aim of our study is to determine whether CsA has a direct effect on mesangial cells and whether the cellular response depends on the genetic background, Methods, We studied mesangial cells isolated from mice susceptible (ROP/Le-+Es1(b)/+Es1(a), ROP) and resistant to glomerulosclerosis (B6SJLF1, C57), We previously showed that sclerosis-prone and sclerosis-resistant phenotypes are maintained in vitro, We examined whether CsA exposure directly affected extracellular matrix turnover in mesangial cells and whether the response is determined by the genetic background, Extracellular matrix synthesis and degradation were studied by proline incorporation, ELISA, reverse transcription-polymerase chain reaction, zymography, and reverse zymography, We chose a CsA dose that induced neither cytotoxicity nor apoptosis (1 mu g/ml), Results. At the dose of 1 mu g/ml total collagen accumulation was increased in ROP but not in C57 cells. Matrix metalloproteinase (MMP)-2 activity and mRNA levels were selectively decreased in ROP cells, CsA exposure did not affect tissue inhibitors of MMP (TIMP)-1 and -2 activity or TGF-beta(1) mRNA expression and protein synthesis in either cell line. Conclusion. CsA increases total collagen accumulation in mesangial cells from sclerosis-prone mice by decreasing MMP-2 activity, but does not affect cells from sclerosis-resistant mice. Thus, CsA directly affects mesangial cells, but only those with a permissive genetic background for glomerulosclerosis.
引用
收藏
页码:587 / 593
页数:7
相关论文
共 34 条
[1]   Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro - TIMP-3 promotes apoptosis [J].
Baker, AH ;
Zaltsman, AB ;
George, SJ ;
Newby, AC .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (06) :1478-1487
[2]   STUDIES ON BINDING AND MITOGENIC EFFECT OF INSULIN AND INSULIN-LIKE GROWTH FACTOR-I IN GLOMERULAR MESANGIAL CELLS [J].
CONTI, FG ;
STRIKER, LJ ;
LESNIAK, MA ;
MACKAY, K ;
ROTH, J ;
STRIKER, GE .
ENDOCRINOLOGY, 1988, 122 (06) :2788-2795
[3]   SYNTHESIS AND RELEASE OF INSULINLIKE GROWTH FACTOR-I BY MESANGIAL CELLS IN CULTURE [J].
CONTI, FG ;
STRIKER, LJ ;
ELLIOT, SJ ;
ANDREANI, D ;
STRIKER, GE .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (06) :F1214-F1219
[4]   Additive effect of cyclosporine and low density lipoproteins on transforming growth factor-β1 and monocyte chemotactic protein-1 expression in human mesangial cells [J].
Di Paolo, S ;
Grandaliano, G ;
Gesualdo, L ;
Ranieri, E ;
Schena, FP .
TRANSPLANTATION PROCEEDINGS, 1998, 30 (05) :2051-2051
[5]   COLLAGEN BIOSYNTHESIS DURING CONNECTIVE-TISSUE DEVELOPMENT IN CHICK-EMBRYO [J].
DIEGELMANN, RF ;
PETERKOFSKY, B .
DEVELOPMENTAL BIOLOGY, 1972, 28 (03) :443-+
[6]   Inhibition of the matrix metalloproteinase system in a rat model of chronic cyclosporine nephropathy [J].
Duymelinck, C ;
Deng, JT ;
Dauwe, SEH ;
De Broe, ME ;
Verpooten, GA .
KIDNEY INTERNATIONAL, 1998, 54 (03) :804-818
[7]   Nature and severity of the glomerular response to nephron reduction is strain-dependent in mice [J].
Esposito, C ;
He, CJ ;
Striker, GE ;
Zalups, RK ;
Striker, LJ .
AMERICAN JOURNAL OF PATHOLOGY, 1999, 154 (03) :891-897
[8]   Progressive histologic injury in kidneys from heart and liver transplant recipients receiving cyclosporine [J].
Falkenhain, ME ;
Cosio, FG ;
Sedmak, DD .
TRANSPLANTATION, 1996, 62 (03) :364-370
[9]   CYCLOSPORINE ENHANCES THE SYNTHESIS OF SELECTED EXTRACELLULAR-MATRIX PROTEINS BY RENAL-CELLS IN CULTURE - DIFFERENT CELL RESPONSES AND PHENOTYPE CHARACTERIZATION [J].
GHIGGERI, GM ;
ALTIERI, P ;
OLEGGINI, R ;
VALENTI, F ;
GINEVRI, F ;
PERFUMO, F ;
GUSMANO, R .
TRANSPLANTATION, 1994, 57 (09) :1382-1388
[10]   RELATIONSHIPS BETWEEN MESANGIAL CELL-PROLIFERATION AND TYPE-I AND TYPE-IV COLLAGEN MESSENGER-RNA LEVELS IN-VITRO [J].
HE, CJ ;
STRIKER, LJ ;
TSOKOS, M ;
YANG, CW ;
PETEN, EP ;
STRIKER, GE .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1995, 269 (03) :C554-C562