Implication of Bcl-2-associated athanogene 3 in fibroblast growth factor-2-mediated epithelial-mesenchymal transition in renal epithelial cells.

Abstract

The epithelial-mesenchymal transition (EMT) of tubular epithelial cells to myofibroblast-like cells plays a substantial role in renal tubulointerstitial fibrosis, which is a common pathological character of end-stage renal disease (ESRD). Fibroblast growth factor-2 (FGF-2) triggers EMT in tubular epithelial cells and increases Bcl-2-associated athanogene 3 (BAG3) expression in neural progenitor and neuroblastoma cells. In addition, a novel role of regulation of EMT has been ascribed to BAG3 recently. These previous reports urged us to study the potential involvement of BAG3 in EMT triggered by FGF-2 in renal tubular epithelial cells. The current study found that FGF-2 induced EMT, simultaneously increased BAG3 expression in human kidney 2 (HK2) cells. Although FGF-2 induced EMT in nontransfected or scramble short hairpin RNA (shRNA) transfected HK2 cells, it was ineffective in BAG3-silenced cells, indicating a favorable role of BAG3 in EMT of tubular cells induced by FGF-2. Knockdown of BAG3 also significantly suppressed motion and invasion of HK2 cells mediated by FGF-2. Furthermore, we confirmed that BAG3 was upregulated in kidney of unilateral ureteral obstruction (UUO) rats, a well-established renal fibrosis model, in which EMT is supposed to exert a substantial influence on renal fibrosis. Importantly, upregulation of BAG3 was limited to tubular epithelial cells. Results of the current study identify BAG3 as a potential player in EMT of tubular epithelial cells, as well as renal fibrosis.

• Authors: Feng Du, Si Li, Tian Wang, Hai-Yan Zhang, De-Tian Li, Zhen-Xian Du, Hua-Qin Wang
• Journal: Experimental biology and medicine (Maywood, N.J.) (Exp Biol Med (Maywood)) Vol. 240 Issue 5 Pg. 566-75 (May 2015) ISSN: 1535-3699 [Electronic] England
• PMID: 25361773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by the Society for Experimental Biology and Medicine.

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAG3 protein, human
• Biomarkers
• Fibroblast Growth Factor 2

Topics

• Adaptor Proteins, Signal Transducing (physiology)
• Apoptosis Regulatory Proteins (physiology)
• Biomarkers (metabolism)
• Cell Line
• Epithelial Cells (cytology)
• Epithelial-Mesenchymal Transition (physiology)
• Fibroblast Growth Factor 2 (physiology)
• Humans
• Kidney (cytology, metabolism)
• Real-Time Polymerase Chain Reaction