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Titolo:
Glial cell line-derived neurotrophic factor (GDNF) is expressed in the human kidney and is a growth factor for human mesangial cells
Autore:
Orth, SR; Ritz, E; Suter-Crazzolara, C;
Indirizzi:
Univ Heidelberg, Med Klin, Sekt Nephrol, Dept Internal Med, D-69115 Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-69115 , D-69115 Heidelberg, Germany Univ Heidelberg, Dept Anat & Cell Biol 3, D-69115 Heidelberg, Germany UnivHeidelberg Heidelberg Germany D-69115 , D-69115 Heidelberg, Germany
Titolo Testata:
NEPHROLOGY DIALYSIS TRANSPLANTATION
fascicolo: 5, volume: 15, anno: 2000,
pagine: 589 - 595
SICI:
0931-0509(200005)15:5<589:GCLNF(>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
MICE LACKING GDNF; FACTOR-BETA; TYROSINE KINASE; TRANSFORMING GROWTH-FACTOR-BETA-1; EXPERIMENTAL GLOMERULONEPHRITIS; EXTRACELLULAR-MATRIX; ANGIOTENSIN-II; MESSENGER-RNA; RET RECEPTOR; IN-VITRO;
Keywords:
glial cell line-derived neurotrophic factor; glomerulosclerosis; kidney; mesangial cell proliferation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Orth, SR Univ Heidelberg, Med Klin, Sekt Nephrol, Dept Internal Med, Bergheimer Str56A, D-69115 Heidelberg, Germany Univ Heidelberg Bergheimer Str 56A Heidelberg Germany D-69115 ny
Citazione:
S.R. Orth et al., "Glial cell line-derived neurotrophic factor (GDNF) is expressed in the human kidney and is a growth factor for human mesangial cells", NEPH DIAL T, 15(5), 2000, pp. 589-595

Abstract

Background. Glial cell line-derived neurotrophic factor (GDNF), a recentlycloned member of the transforming growth factor-beta (TGF-beta) superfamily, is a potent neurotrophic factor in vitro and in vivo. GDNF is essential for nephrogenesis and the highest expression of GDNF is found in the developing kidney. Increased plasma GDNF levels have recently been documented in patients with chronic renal failure; the source and role of this increase, however, remain unclear. No data are available about the expression of GDNFin human adult kidney or human adult mesangial cell (HMC) cultures. We hypothesized that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor in the pathogenesis of glomerulosclerosis. Methods. To address this hypothesis, we first investigated (by RT-PCR) theexpression of GDNF mRNA and the mRNAs of the GDNF receptors Ret and GFR alpha-1 in (i) adult human renal cortex and medulla and (ii) in HMC in culture. The results were compared to the expression of these molecules in different developmental stages of the rat kidney. We found that both GDNF and itsreceptors were expressed in human adult kidney and HMC. Since this findingimplicates a role for GDNF beyond nephrogenesis, i.e. in renal physiology/pathophysiology, we investigated the effect of GDNF on HMC growth, i.e. (i)cellular protein synthesis as an index of hypertrophy ([H-3]methionine incorporation), (ii) DNA synthesis ([H-3]thymidine incorporation) and cell proliferation (cell numbers) as indices of hyperplasia, and (iii) extracellular matrix synthesis, i.e. collagenous and non-collagenous extracellular proteins ([H-3]proline incorporation into the collagenase-sensitive and -insensitive fraction). HMC cultures were used as a surrogate model for the development of glomerulosclerosis. Results. GDNF induced a biphasic growth stimulatory effect in HMC with stimulation at the lowest concentration used (2 ng/ml) but had no effect at higher concentrations (20 and 50 ng/ml). In contrast, cellular protein synthesis and extracellular matrix synthesis were significantly and dose-dependently increased by GDNF. Conclusions. These results suggest that GDNF, similar to other members of the TGF-beta superfamily, might play a role as a growth factor for mesangial cells and might thus be a player in the pathogenesis of glomerulosclerosis.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 14/08/20 alle ore 16:02:52