Abstract |
P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. In the present study, we constructed a recombinant adenovirus vector of p311 (called Ad-P311) and transferred it into rat renal proximal tubular epithelial cells (NRK-52E) to explore the effect of P311 on epithelial-mesenchymal transition (EMT) of NRK-52E cells induced by TGF-β1 and to elucidate its underlying mechanism against EMT. After successfully construction of Ad-P311 and transfer into NRK-52E cells, the proliferation and growth of P311-expressing cells was detected by MTT assay. TGF-β1 was used to induce NRK-52E cells and Western blot analysis was used to examine the EMT markers ( E-cadherin and α-smooth muscle actin (α-SMA)), signal transducers (p-Smad2/3 and Smad7). Integrin Linked Kinase (ILK) as a key intracellular mediator that controls TGF-β1-induced-EMT was also assayed by Western blot analysis. The results showed that P311 transfection could significantly inhibit the proliferation and growth of TGF-β1 induced NRK-52E cells. The results also showed that TGF-β1 could induce EMT in NRK-52E cells through Smad-ILK signaling pathway with an increase in α-SMA, pSmad2/3 and ILK expression, and a decrease in E-cadherin and Smad7 expression. However, P311 efficiently blocked Smad-ILK pathway activation and attenuated all these EMT changes induced by TGF-β1. These findings suggest that P311 might be involved in the pathogenesis of renal fibrosis by inhibiting the EMT process via TGF-β1-Smad-ILK pathway. P311 might be a novel target for the control of renal fibrosis and the progression of CKD.
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Authors | Fanghua Qi, Pingping Cai, Xiang Liu, Min Peng, Guomin Si |
Journal | Bioscience trends
(Biosci Trends)
Vol. 9
Issue 5
Pg. 299-306
(Oct 2015)
ISSN: 1881-7823 [Electronic] Japan |
PMID | 26559022
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Nerve Tissue Proteins
- Nrep protein, rat
- Smad Proteins
- Tgfb1 protein, rat
- Transforming Growth Factor beta1
- integrin-linked kinase
- Protein Serine-Threonine Kinases
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Topics |
- Adenoviridae
- Animals
- Epithelial-Mesenchymal Transition
- Genetic Vectors
- HEK293 Cells
- Humans
- Nephrosclerosis
(etiology, metabolism)
- Nerve Tissue Proteins
(genetics, metabolism)
- Protein Serine-Threonine Kinases
(metabolism)
- Rats
- Smad Proteins
(metabolism)
- Transforming Growth Factor beta1
(metabolism)
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