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学科主题: 临床医学
题名:
ERK-dependent signaling pathway and transcriptional factor Ets-1 regulate matrix metalloproteinase-9 production in transforming growth factor-beta 1 stimulated glomerular podocytes
作者: Liu, SY; Liang, Y; Huang, HC; Wang, LZ; Li, YQ; Li, JZ; Li, XM; Wang, HY
关键词: transforming growth factor beta 1 ; matrix metalloproteinase ; signaling pathway ; glomerulosclerosis ; Ets-1
刊名: CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
发表日期: 2005
卷: 16, 期:4-6, 页:207-216
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell Biology ; Physiology
研究领域[WOS]: Cell Biology ; Physiology
关键词[WOS]: GROWTH-FACTOR-BETA ; EXPERIMENTAL DIABETIC-NEPHROPATHY ; ACTIVATED PROTEIN-KINASE ; FACTOR-KAPPA-B ; EPITHELIAL-CELLS ; TGF-BETA ; MATRIX METALLOPROTEINASES ; MESANGIAL CELLS ; TRANSFORMED KERATINOCYTES ; MEMBRANOUS NEPHROPATHY
英文摘要:

The unregulated synthesis of glomerular basement membrane (GBM) components, extracelluar matrix (ECM) proteins, or the secretion of ECM-degradation enzymes, matrix metalloproteinases ( MMPs), by podocytes under pathological conditions might be major factors in GBM damage. The present study examined the effects and the underlying molecular mechanism of transforming growth factor beta 1 (TGF beta 1) on the production of gelatinase in cultured murine podocytes. Our results showed that TGF beta 1 is the most potent inducer of MMP-9 secretion in both a dose- and time-dependent manner, but has very little effect on MMP-2 secretion. TGF beta 1 upregulated MMP-9 mRNA levels, but did not affect the expression of matrix mettaloproteinases TIMP-1 mRNA. TGF beta 1 induced activation of both Smad2 and extracellular signal-regulated kinases (ERK1/2). However, blockade of Smad2 signaling pathway by Staurosporine did not affect the TGF beta 1-stimulated secretion of MMP-9, whereas inhibition of activation of ERK1/2 by PD98059 abolished TGF beta 1-stimulated secretion of MMP-9 and expression of MMP-9 mRNA. Protein levels of the transcriptional factor Ets-1 increased and were sustained for 12 h by TGF beta 1-stimulation. Our data also showed that blockage of ERK1/2 activation by PD98059 led to a reduction in the level of Ets-1 protein and to a consequent decrease in MMP-9 mRNA levels. These results demonstrate that TGF beta 1 can induce the production of MMP-9 in podocytes through the ERK1/2 MAPK pathway, and suggested that an increase in MMP-9 enzymatic activities may be involved in the damage of the GBM in response to inflammatory factors, ultimately leading to glomerulosclerosis.

语种: 英语
WOS记录号: WOS:000233363700007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61356
Appears in Collections:北京大学第一临床医学院_肾脏内科_期刊论文

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作者单位: Peking Univ, Div Nephrol, Beijing 100034, Peoples R China

Recommended Citation:
Liu, SY,Liang, Y,Huang, HC,et al. ERK-dependent signaling pathway and transcriptional factor Ets-1 regulate matrix metalloproteinase-9 production in transforming growth factor-beta 1 stimulated glomerular podocytes[J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,2005,16(4-6):207-216.
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