Dietary nobiletin suppresses TGF-β1-Src-caveolin-1 dependent signaling involved with high glucose-induced renal mesangial matrix accumulation / 한국영양학회지
Journal of Nutrition and Health
;
: 1-12, 2020.
Article
in Korean
| WPRIM
| ID: wpr-811256
ABSTRACT
PURPOSE:
Diabetic nephropathy is one of the most important diabetic complications prompted by chronic hyperglycemia, characterized by glomerulosclerosis, tubular fibrosis, and it eventually causes kidney failure. Nobiletin is a polymethoxyflavone present in tangerine and other citrus peels, and has anti-cancer and anti-inflammatory effects. This study investigated the effects of nobiletin on glomerular fibrosis through inhibition of the transforming growth factor (TGF)-β1-Src-caveolin-1 pathway.METHODS:
Human renal mesangial cells (HRMC) were incubated in media containing 33 mM glucose with or without 1–20 uM nobiletin for 3 day. The cellular expression levels of fibrogenic collagen IV, fibronectin, connective tissue growth factor (CTGF), TGF-β1, Src and caveolin-1 were all examined. In addition, TGF-β1, Src and caveolin-1 proteins were screened to reveal the relationship among TGF-β1-Src-caveolin-1 signaling in glomerular fibrosis.RESULTS:
High glucose promoted the production of collagen IV, fibronectin and CTGF in HRMC, which was inhibited in a dose dependent manner by 1–20 uM nobiletin. The Western blot data showed that high glucose elevated the expression of TGF-β1, Src, caveolin-1 and Rho GTPase. When nobiletin was treated to the HRMC exposed to high glucose, the expression of TGF-β1-Src-caveolin-1 was dampened. Finally, TGF-β1-Src-caveolin-1 signaling pathway was activated in high glucose-exposed HRMC, and such activation was encumbered by nobiletin.CONCLUSION:
These result demonstrated that nobiletin blunted high glucose-induced extracellular matrix accumulation via inhibition of the TGF-β1-Src-caveolin-1 related intracellular signaling pathway. Nobiletin may be a potent renoprotective agent to counteract diabetes-associated glomerular fibrosis that leads to kidney failure.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Fibrosis
/
Transforming Growth Factors
/
Blotting, Western
/
Collagen
/
Fibronectins
/
Citrus
/
Diabetes Complications
/
Diabetic Nephropathies
/
Mesangial Cells
/
Renal Insufficiency
Limits:
Humans
Language:
Korean
Journal:
Journal of Nutrition and Health
Year:
2020
Type:
Article
Similar
MEDLINE
...
LILACS
LIS