Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro

被引：129

作者：

Zheng, Chun-Xia ^{[1
]}

Chen, Zhao-Hong ^{[1
]}

Zeng, Cai-Hong ^{[1
]}

Qin, Wei-Song ^{[1
]}

Li, Lei-Shi ^{[1
]}

Liu, Zhi-Hong ^{[1
]}

机构：

[1] Nanjing Univ, Sch Med, Jinling Hosp, Res Inst Nephrol, Nanjing 210002, Peoples R China

来源：

KIDNEY INTERNATIONAL | 2008年 / 74卷 / 05期

关键词：

triptolide; puromycin aminonucleoside; proteinuria; podocyte;

D O I：

10.1038/ki.2008.203

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Extracts of Tripterygium wilfordii Hook F have been used to treat glomerulonephritis for more than 30 years in China with dramatic antiproteinuric effects. Triptolide, a diterpene triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.

引用

页码：596 / 612

页数：17

共 45 条

[11]

He Qihua, 2003, Beijing Da Xue Xue Bao Yi Xue Ban, V35, P252

[12] Oxidative stress-induced actin reorganization mediated by the p38 mitogen-activated protein kinase heat shock protein 27 pathway in vascular endothelial cells [J].

Huot, J ;

Houle, F ;

Marceau, F ;

Landry, J .

CIRCULATION RESEARCH, 1997, 80 (03) :383-392

[13] Actin filament organization of foot processes in rat podocytes [J].

Ichimura, K ;

Kurihara, H ;

Sakai, T .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2003, 51 (12) :1589-1600

[14] Clinical impact of research on the podocyte slit diaphragm [J].

Johnstone, DB ;

Holzman, LB .

NATURE CLINICAL PRACTICE NEPHROLOGY, 2006, 2 (05) :271-282

[15] Cloning of rat nephrin: Expression in developing glomeruli and in proteinuric states [J].

Kawachi, H ;

Koike, H ;

Kurihara, H ;

Yaoita, E ;

Orikasa, M ;

Shia, MA ;

Sakai, T ;

Yamamoto, T ;

Salant, DJ ;

Shimizu, F .

KIDNEY INTERNATIONAL, 2000, 57 (05) :1949-1961

[16] Triptolide inhibits murine-inducible nitric oxide synthase expression by down-regulating lipopolysaccharide-induced activity of nuclear factor-κB and c-Jun NH2-terminal kinase [J].

Kim, YH ;

Lee, SH ;

Lee, JY ;

Choi, SW ;

Park, JW ;

Kwon, TK .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 494 (01) :1-9

[17] Mechanism of the process formation; Podocytes vs. neurons [J].

Kobayashi, N .

MICROSCOPY RESEARCH AND TECHNIQUE, 2002, 57 (04) :217-223

[18] Process formation of the renal glomerular podocyte: Is there common molecular machinery for processes of podocytes and neurons? [J].

Kobayashi N. ;

Gao S.-Y. ;

Chen J. ;

Saito K. ;

Miyawaki K. ;

Li C.-Y. ;

Pan L. ;

Saito S. ;

Terashita T. ;

Matsuda S. .

Anatomical Science International, 2004, 79 (1) :1-10

[19] Role of p38 mitogen-activated protein kinase activation in podocyte injury and proteinuria in experimental nephrotic syndrome [J].

Koshikawa, M ;

Mukoyama, M ;

Mori, K ;

Suganami, T ;

Sawai, K ;

Yoshioka, T ;

Nagae, T ;

Yokoi, H ;

Kawachi, H ;

Shimizu, F ;

Sugawara, A ;

Nakao, K .

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2005, 16 (09) :2690-2701

[20]

Li L., 1981, CHINESE J INTERN MED, V20, P216

← 1 2 3 4 5 →