Cargando…
Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling
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 trans...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487264/ https://www.ncbi.nlm.nih.gov/pubmed/30926678 http://dx.doi.org/10.1042/BSR20182293 |
_version_ | 1783414467448537088 |
---|---|
author | Chen, Hong-Min Dai, Jia-Jia Zhu, Rui Peng, Fang-Fang Wu, Su-Zhen Yu, Hong Krepinsky, Joan C. Zhang, Bai-Fang |
author_facet | Chen, Hong-Min Dai, Jia-Jia Zhu, Rui Peng, Fang-Fang Wu, Su-Zhen Yu, Hong Krepinsky, Joan C. Zhang, Bai-Fang |
author_sort | Chen, Hong-Min |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6487264 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64872642019-05-09 Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling Chen, Hong-Min Dai, Jia-Jia Zhu, Rui Peng, Fang-Fang Wu, Su-Zhen Yu, Hong Krepinsky, Joan C. Zhang, Bai-Fang Biosci Rep Research Articles 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. Portland Press Ltd. 2019-04-26 /pmc/articles/PMC6487264/ /pubmed/30926678 http://dx.doi.org/10.1042/BSR20182293 Text en © 2019 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Chen, Hong-Min Dai, Jia-Jia Zhu, Rui Peng, Fang-Fang Wu, Su-Zhen Yu, Hong Krepinsky, Joan C. Zhang, Bai-Fang Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling |
title | Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling |
title_full | Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling |
title_fullStr | Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling |
title_full_unstemmed | Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling |
title_short | Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling |
title_sort | parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/src/egfr signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6487264/ https://www.ncbi.nlm.nih.gov/pubmed/30926678 http://dx.doi.org/10.1042/BSR20182293 |
work_keys_str_mv | AT chenhongmin parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling AT daijiajia parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling AT zhurui parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling AT pengfangfang parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling AT wusuzhen parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling AT yuhong parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling AT krepinskyjoanc parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling AT zhangbaifang parathyroidhormonerelatedproteininducesfibronectinupregulationinratmesangialcellsthroughreactiveoxygenspeciessrcegfrsignaling |