Epigallocatechin-3-gallate reduces tubular cell apoptosis in mice with ureteral obstruction.
BACKGROUND
Tubular cell apoptosis plays a crucial role in different kinds of renal diseases. Epigallocatechin-3-gallate (EGCG), a polyphenol extracted from green tea, has been shown to inhibit renal fibrosis in unilateral ureteral obstruction (UUO) mice, but its role in preventing tubular cell apoptosis and the underlying signaling mechanisms still remains unclear.


METHODS
Mice subjected to UUO were intraperitoneally administered EGCG (5 mg/kg) for 14 d. Normal rat kidney proximal tubular epithelial cell line NRK-52E was induced by transforming growth factor β1 (TGF-β1). Periodic acid-schiff and Masson's trichrome staining was used for histologic study. TUNEL, Hoechst staining, and flow cytometry analysis were used to measure the apoptotic status of tubular cells. Western blotting was used to determine the expression of apoptotic-associated proteins and mitogen-activated protein kinase pathway proteins.


RESULTS
EGCG significantly attenuated tubular injury and renal tubulointerstitial fibrosis in the obstructed kidneys of UUO mice. In addition, EGCG prevented UUO and TGF-β1-induced tubular apoptosis in a dose-dependent manner. In parallel, protein expression of B-clell lymphoma-2 (Bcl-2) was upregulated and protein expressions of Bcl-2 accosiated X protein (Bax), cleaved caspase 3, and cleaved poly ADP-ribose polymerase (PARP) were downregulated by EGCG. Furthermore, UUO and TGF-β1-stimulated phosphorylation of mitogen-activated protein kinase was inhibited by EGCG.


CONCLUSIONS
EGCG effectively reduces tubular cell apoptosis induced by UUO and may have potential as a clinical treatment in patients with chronic kidney disease.
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Yanqiu
Y
Wang
Department of Nephrology, Ordos Central Hospital, Ordos, Inner Mongolia, People's Republic of China.
Na
N
Liu
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Xiaohui
X
Bian
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Guangping
G
Sun
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Feng
F
Du
Department of Laboratory Medicine, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Bowen
B
Wang
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China.
Xuesong
X
Su
Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, People's Republic of China. Electronic address: lidt@sj-hospital.org.
Detian
D
Li
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D014517:Ureteral Obstruction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D015415:Biomarkers; D020011:Protective Agents; D002392:Catechin; C045651:epigallocatechin gallate
Apoptosis; EGCG; MAPK; Tubular cell; UUO mice