Bibliographic Details
| Title: |
Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling. |
| Authors: |
Hong-Min Chen1 (AUTHOR), Jia-Jia Dai1 (AUTHOR), Rui Zhu1 (AUTHOR), Fang-Fang Peng1 (AUTHOR), Su-Zhen Wu2 (AUTHOR), Hong Yu1 (AUTHOR), Krepinsky, Joan C.3 (AUTHOR), Bai-Fang Zhang1 (AUTHOR) zbfwq@whu.edu.cn |
| Source: |
Bioscience Reports. 4/30/2019, Vol. 39 Issue 4, p1-16. 16p. 1 Diagram, 1 Chart, 8 Graphs. |
| Abstract: |
Parathyroid hormone-related protein (PTHrP) is known to be up-regulated in both glomeruli and tubules in patients with diabetic kidney disease (DKD), but its role remains unclear. Previous studies show that PTHrP-induced hypertrophic response in mesangial cells (MCs) and epithelial-mesenchymal transition (EMT) in tubuloepithelial cells can be mediated by TGF-β1. In the present study, although long-term PHTrP (1–34) treatment increased the mRNA and protein level of TGF-β1 in primary rat MCs, fibronectin up-regulation occurred earlier, suggesting that fibronectin induction is independent of TGF-β1/Smad signaling. We thus evaluated the involvement of epidermal growth factor receptor (EGFR) signaling and found that nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species mediates PTHrP (1–34)-induced Src kinase activation. Src phosphorylates EGFR at tyrosine 845 and then transactive EGFR. Subsequent PI3K activation mediates Akt and ERK1/2 activation. Akt and ERK1/2 discretely lead to excessive protein synthesis of fibronectin. Our study thus demonstrates the new role of PTHrP in fibronectin up-regulation for the first time in glomerular MCs. These data also provided new insights to guide development of therapy for glomerular sclerosis. [ABSTRACT FROM AUTHOR] |
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| Database: |
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