Blocking protein phosphatase 2A signaling prevents endothelial-to-mesenchymal transition and renal fibrosis: a peptide-based drug therapy

• DOI: 10.1038/srep19821
• Publication Date: 2016-01-25T12:38:52Z
• Authors: Yuanjun Deng; Yanyan Guo; Ping Liu; Rui Zeng; Yong Ning; Guangchang Pei; Yueqiang Li; Meixue Chen; Shuiming Guo; Xiaoqing Li; Min Han; Gang Xu
• Keywords: 0301 basic medicine; 0303 health sciences; Epithelial-Mesenchymal Transition; Cell-Penetrating Peptides; Fibroblasts; Kidney; Fibrosis; Article; Transforming Growth Factor beta1; Disease Models, Animal; Mice; 03 medical and health sciences; Gene Expression Regulation; Animals; Humans; Endothelium; Protein Phosphatase 2; Signal Transduction

Endothelial-to-mesenchymal transition (EndMT) contributes to the emergence of fibroblasts and plays a significant role in renal interstitial fibrosis. Protein phosphatase 2A (PP2A) is major serine/threonine protein eukaryotic cells regulates many signaling pathways. However, significance PP2A EndMT poorly understood. In present study, was evaluated. We demonstrated that activated endothelial (EC) during their phenotype acquisition mouse model obstructive nephropathy (i.e., UUO). Inhibition activity by its specific inhibitor prevented EC undergoing EndMT. Importantly, activation dependent on tyrosine nitration at 127 catalytic subunit (PP2Ac). Our renal-protective strategy block tyrosine127 inhibit using mimic peptide derived from PP2Ac conjugating cell penetrating (CPP: TAT), termed TAT-Y127WT. Pretreatment with TAT-Y127WT able prevent TGF-β1-induced Administration UUO mice significantly ameliorated level, preserved density peritubular capillaries reduction extracellular matrix deposition. Taken together, these results suggest inhibiting potential preventive for