Knockdown of fibronectin induces mitochondria-dependent apoptosis in rat mesangial cells.
Di Wu,Xiangmei Chen,Deng-Fu Guo,Quan Hong,Bo Fu,Rui Ding,Lifang Yu,Kai Hou,Zhe Feng,Xiaojie Zhang,Jianzhong Wang +10 more
TLDR
Two studies explored a new method for simultaneously inhibiting MC proliferation and ECM accumulation, which may represent a novel therapeutic approach to glomerulosclerosis.Abstract:
Extracellular matrix (ECM) expansion and mesangial cell (MC) proliferation are prominent features of most types of glomerulosclerosis. A delicate balance between the ECM and MC regulates cell survival. Increasing evidence shows that a loss of ECM components can cause mitochondrial dysfunction and induce cell apoptosis. It is proposed that directly blocking the synthesis of ECM components could lighten ECM accumulation and suppress cell overproliferation status. Fibronectin, one of the predominant adhesive glycoproteins of the mesangial ECM, provides the survival signal for cells. Its accumulation can be observed in most types of glomerulosclerosis. In this study, angiotensin II-induced fibronectin was suppressed by an RNA interference technique. It is interesting that MC slowly underwent apoptosis after infection with a retrovirus that continuously suppressed fibronectin synthesis. It was found that MC apoptosis occurred in a mitochondria-dependent manner mainly as a result of cytochrome c release and downstream caspase-3 and -9 activation. Furthermore, it was demonstrated that fibronectin knockdown affected mitochondrial handling of Ca 2+ release from the endoplasmic reticulum. Importantly, blocking the inositol 1,4,5-triphosphate receptor with, 3,4,5-trimethoxybenzoate or decreasing Ca 2+ in the ECM with EGTA partially saved the cells from apoptosis. These studies, which explored a new method for simultaneously inhibiting MC proliferation and ECM accumulation, may represent a novel therapeutic approach to glomerulosclerosis.read more
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From Mitochondria to Disease: Role of the Renin-Angiotensin System
TL;DR: This review intends to present available information pointing to mitochondria as targets for therapeutic Ang-II blockade in human renal and CV disease, and provide a new perspective on the implications that RAS-blockade can offer as a therapeutic strategy.
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Angiotensin II, mitochondria, cytoskeletal, and extracellular matrix connections: an integrating viewpoint.
TL;DR: It is hypothesized that the depression of mitochondrial energy metabolism brought about by Angiotensin II is preceded by ANG II-induced integrin signaling and the consequent derangement of the cytoskeletal filament network and/or ECM organization.
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FoxM1 is associated with poor prognosis of non-small cell lung cancer patients through promoting tumor metastasis.
Nuo Xu,Deshui Jia,Wenfeng Chen,Hao Wang,Fanglei Liu,Haiyan Ge,Xiaodan Zhu,Yuanlin Song,Xin Zhang,David Y. Zhang,Di Ge,Chunxue Bai +11 more
TL;DR: It is suggested that FoxM1 overexpression in tumor tissues is significantly associated with the poor prognosis of NSCLC patients through promoting tumor metastasis through inducing epithelial-mesenchymal transition (EMT) program.
Journal ArticleDOI
Development of a highly metastatic model that reveals a crucial role of fibronectin in lung cancer cell migration and invasion
Deshui Jia,Mingxia Yan,Xiaomin Wang,Xiangfang Hao,Linhui Liang,Lei Liu,Hanwei Kong,Xianghuo He,Jinjun Li,Ming Yao +9 more
TL;DR: A new lung cancer cell line with highly metastatic potentials, which is subject to EMT and possibly mediated by increased fibronectin expression is established, which can be used to identify underlying mechanisms of lung cancer metastasis.
Journal ArticleDOI
Downregulation of Connexin 43 Expression by High Glucose Induces Senescence in Glomerular Mesangial Cells
Xiaojie Zhang,Xiangmei Chen,Di Wu,Weiping Liu,Jianzhong Wang,Zhe Feng,Guangyan Cai,Bo Fu,Quan Hong,Jing Du +9 more
TL;DR: It is demonstrated for the first time that downregulation of Cx43 expression by high glucose promotes the senescence of GMC, which may be involved in the pathogenesis of diabetic nephropathy.
References
More filters
Journal ArticleDOI
Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells
TL;DR: 21-nucleotide siRNA duplexes provide a new tool for studying gene function in mammalian cells and may eventually be used as gene-specific therapeutics.
Journal ArticleDOI
A System for Stable Expression of Short Interfering RNAs in Mammalian Cells
TL;DR: It is shown that siRNA expression mediated by this vector causes efficient and specific down-regulation of gene expression, resulting in functional inactivation of the targeted genes.
Journal ArticleDOI
Disruption of epithelial cell-matrix interactions induces apoptosis
Steven M. Frisch,Hunter Francis +1 more
TL;DR: It is demonstrated that apoptosis was induced by disruption of the interactions between normal epithelial cells and extracellular matrix, and the circumvention of anoikis accompanies the acquisition of anchorage independence or cell motility.
Journal ArticleDOI
RNAi: Double-Stranded RNA Directs the ATP-Dependent Cleavage of mRNA at 21 to 23 Nucleotide Intervals
TL;DR: It is found that RNAi is ATP dependent yet uncoupled from mRNA translation, suggesting that the 21-23 nucleotide fragments from the dsRNA are guiding mRNA cleavage.
Journal ArticleDOI
The mitochondrial death/life regulator in apoptosis and necrosis
TL;DR: The acquisition of the biochemical and ultrastructural features of apoptosis critically relies on the liberation of apoptogenic proteases or protease activators from mitochondria.