Back to Search
Start Over
Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling.
- Source :
-
Bioscience reports [Biosci Rep] 2019 Apr 26; Vol. 39 (4). Date of Electronic Publication: 2019 Apr 26 (Print Publication: 2019). - Publication Year :
- 2019
-
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.<br /> (© 2019 The Author(s).)
- Subjects :
- Animals
Diabetic Nephropathies pathology
Epithelial-Mesenchymal Transition genetics
ErbB Receptors genetics
Fibronectins biosynthesis
Humans
Kidney Glomerulus pathology
Kidney Tubules metabolism
Kidney Tubules pathology
MAP Kinase Signaling System genetics
Mesangial Cells metabolism
Mesangial Cells pathology
Parathyroid Hormone-Related Protein metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt genetics
Rats
Reactive Oxygen Species metabolism
Transforming Growth Factor beta1 genetics
src-Family Kinases genetics
Diabetic Nephropathies genetics
Fibronectins genetics
Kidney Glomerulus metabolism
Parathyroid Hormone-Related Protein genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1573-4935
- Volume :
- 39
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Bioscience reports
- Publication Type :
- Academic Journal
- Accession number :
- 30926678
- Full Text :
- https://doi.org/10.1042/BSR20182293