Rhein inhibits renal tubular epithelial cell hypertrophy and extracellular matrix accumulation induced by transforming growth factor beta1.
OBJECTIVE
To investigate the effects of rhein on cell hypertrophy and accumulation of extracellular matrix (ECM) in the renal tubular epithelial cells.


METHODS
LLC-PK1 cells were incubated with transforming growth factor beta1 (TGFbeta1) 2 microg/L for 24 h to induce cell hypertrophy and production of ECM. To evaluate the effects of rhein on inhibiting the action of TGFbeta1, cell volume, cellular protein level, and [3H]leucine incorporation in LLC-PK1 cells treated with rhein at different concentrations were measured. In addition, the [3H]proline incorporation, level of fibronectin (FN) in supernatant, and mRNA expression of collagen IV and FN were also detected in rhein treated cells.


RESULTS
The cell volume, cellular protein content, and [3H]leucine incorporation were markedly increased in LLC-PK1 cells after TGFbeta1 stimulation as compared with control (P < 0.01), and this TGFbeta1-stimulated cell hypertrophy was ameliorated by rhein. It was observed that TGFbeta1 not only increased the production of FN and [3H]proline incorporation in LLC-PK1 cells (P < 0.01), but also enhanced the mRNA expression of collagen IV and FN. Rhein significantly decreased the protein production and mRNA expression of ECM in LLC-PK1 cells stimulated by TGFbeta1.


CONCLUSIONS
Rhein can inhibit cell hypertrophy and ECM accumulation in LLC-PK1 cells induced by TGFbeta1, which may partly account for the role of rhein in preventing and retarding the progression of diabetic nephropathy.
Guo
X H
XH
Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.
Liu
Z H
ZH
Dai
C S
CS
Li
H
H
Liu
D
D
Li
L S
LS
D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D024141:Collagen Type IV / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis / Q000235:genetics; D006984:Hypertrophy; D007687:Kidney Tubules, Proximal / Q000473:pathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013552:Swine; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1
D000880:Anthraquinones; D024141:Collagen Type IV; D005353:Fibronectins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C020491:rhein