127 70

Cited 0 times in

Leptin stimulates type I collagen production in db/db mesangial cells: Glucose uptake and TGF-bold beta type II receptor expression

Authors
 Dong Cheol Han  ;  Motohide Isono  ;  Sheldon Chen  ;  Alberto Casaretto  ;  Soon Won Hong  ;  Gunter Wolf  ;  Fuad N Ziyadeh 
Citation
 Kidney International, Vol.59(4) : 1315-1323, 2001 
Journal Title
 Kidney International 
ISSN
 0085-2538 
Issue Date
2001
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 and mesangial cells of both nondiabetic db/m and diabetic db/db mice. In db/db mesangial cells, leptin increased 2-deoxy-D-glucose (2DOG) uptake dose dependently and stimulated gene expression of TGF-beta type II receptor (TbetaRII) and alpha1(I) collagen, but not TGF-beta1. Protein production of type I collagen (enzyme-linked immunosorbent assay) was also increased by leptin. Both leptin-stimulated 2DOG uptake and type I collagen production were suppressed by a PI-3K inhibitor, LY294002. Mesangial cells pretreated with leptin exhibited increased responsiveness to exogenous TGF-beta1, as evidenced by 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 TbetaRII and activate the intraglomerular TGF-beta system, which may contribute to the glomerulosclerosis of obesity or type 2 diabetes.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142450
DOI
10.1046/j.1523-1755.2001.0590041315.x
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실)
Yonsei Authors
홍순원(Hong, Soon Won)
사서에게 알리기
  feedback
Files in This Item:
T200102259.pdf Download
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse