Nerve growth factor exposure promotes tubular epithelial–mesenchymal transition via TGF-β1 signaling activation. (June 2015)

• Record Type: Journal Article
• Authors: Vizza, Donatella; Perri, Anna; Toteda, Giuseppina; Lupinacci, Simona; Leone, Francesca; Gigliotti, Paolo; Lofaro, Danilo; La Russa, Antonella; Bonofiglio, Renzo
• Is Part Of: Growth factors. Volume 33:Number 3(2015:Jun.)
• Page Start: 169
• Page End: 180
• Publication Date: 2015-06
• Subjects: Growth factors -- Periodicals; Physiology -- Periodicals; 611
• Languages: English
• ISSNs: 0897-7194

Abstract

<abstract> <title>Abstract</title> <p>Clinical studies showed that renal expression and serum levels of nerve growth factor (NGF) are increased in renal diseases characterized by progressive fibrosis, a pathologic process in which TGF-β1 mediates most of the key events leading to tubular epithelial–mesenchymal transition (EMT). However, the pathogenic role of high NGF levels has not yet been elucidated. In this study, we found that in tubular renal cells, HK-2, NGF transcriptionally up-regulated TGF-β1 expression and secretion and enhanced cell motility by activating EMT markers <italic>via</italic> its receptors, TrkA and p75^NTR. Interestingly, we observed that TGF-β1–SMAD pathway activation and the up-regulation of EMT markers NGF-induced were both prevented when knockdown of TGF-β1 gene occurred and that the pretreatment with an antibody anti-NGF reversed the nuclear translocation of pSMAD3/SMAD4 complex. Collectively, our results demonstrated that NGF promotes renal fibrosis <italic>via</italic> TGF-β1-signaling activation, suggesting that in kidney diseases high NGF serum levels could contribute to worsen renal fibrosis.</p> </abstract>