Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Leptin stimulates type I collagen production in db/db mesangial cells: Glucose uptake and TGF-beta type II receptor expression
Autore:
Han, DC; Isono, M; Chen, S; Casaretto, A; Hong, SW; Wolf, G; Ziyadeh, FN;
Indirizzi:
Univ Penn, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 rtens Div, Philadelphia, PA 19104 USA Univ Penn, Dept Med, Penn Ctr Mol Studies Kidney Dis, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 idney Dis, Philadelphia, PA 19104 USA Univ Hamburg, Dept Med, Div Nephrol & Osteol, Hamburg, Germany Univ Hamburg Hamburg Germany ed, Div Nephrol & Osteol, Hamburg, Germany
Titolo Testata:
KIDNEY INTERNATIONAL
fascicolo: 4, volume: 59, anno: 2001,
pagine: 1315 - 1323
SICI:
0085-2538(200104)59:4<1315:LSTICP>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
MATRIX GENE-EXPRESSION; DIABETIC MICE; PLASMA LEPTIN; OBESE GENE; INSULIN-RECEPTOR; C2C12 MYOTUBES; OB/OB MICE; RAT; ACTIVATION; PROLIFERATION;
Keywords:
glomerulus; glomerulosclerosis; obesity; diabetic nephropathy; progressive renal disease; adipocyte-derived hormone;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Ziyadeh, FN Univ Penn, Renal Electrolyte & Hypertens Div, 700 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA Univ Penn 700 Clin Res Bldg,415 Curie Blvd Philadelphia PA USA 19104
Citazione:
D.C. Han et al., "Leptin stimulates type I collagen production in db/db mesangial cells: Glucose uptake and TGF-beta type II receptor expression", KIDNEY INT, 59(4), 2001, pp. 1315-1323

Abstract

Background. Serum leptin levels correlate with fat cell mass and are elevated in patients with massive obesity and type 2 diabetes mellitus, which are strong risk factors for the development of glomerulosclerosis. We have previously shown in cultured glomerular endothelial cells that leptin stimulates cellular proliferation and expression of the prosclerotic cytokine transforming growth factor-beta1 (TGF-beta1). Although the effect of leptin on the hypothalamus to regulate energy homeostasis is well known, the effect of leptin on the kidney, and specifically on the glomerular mesangial cell, is unclear. Methods. The obese, diabetic db/db mouse, which lacks the functional full-length Ob-Rb leptin receptor, is a suitable model to assess the effects of hyperleptinemia on peripheral tissues that express other receptor isoforms. The effects of leptin on glucose uptake, the TGF-beta system, and type I collagen production were evaluated in db/db mouse mesangial cells in culture. A phosphatidylinositol-3 kinase (PI-3K) inhibitor was used to assess the role of PI-3K in mediating the effects of leptin. Results. A short form of the leptin receptor (Ob-Ra), but not Ob-Rb, was present by reverse transcription-polymerase chain reaction in the kidney andmesangial cells of both nondiabetic db/m and diabetic db/db mice. In db/dbmesangial cells, leptin increased 2-deoxy-D-glucose (2DOG) uptake dose dependently and stimulated gene expression of TGF-P type II receptor (T beta RII) and alpha1(I) collagen, but not TGF-beta1. Protein production of type Icollagen (enzyme-linked immunosorbent assay) was also increased by leptin. Both leptin-stimulated 2DOG uptake and type I collagen production were suppressed by a PI-SK inhibitor, LY294002. Mesangial cells pretreated with leptin exhibited increased responsiveness to exogenous TGF-beta1, as evidencedby a greater production of type I collagen protein in leptin-pretreated cells exposed to low-dose TGF-beta1 (0.5 ng/mL). The addition of both TGF-beta1 (2 ng/mL) and leptin (100 ng/mL) increased type I collagen production more than addition of either TGF-beta1 or leptin alone. Conclusions. Leptin increases glucose uptake and type I collagen in db/db mesangial cells through a PI-3K-dependent pathway. We postulate that increased leptin levels may transmit a signal through the short-form leptin receptor to up-regulate T beta RII and activate the intraglomerular TGF-beta system, which may contribute to the glomerulosclerosis of obesity or type 2 diabetes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/01/20 alle ore 09:31:56