Faculty Opinions recommendation of TGF-β1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in cultured mouse podocytes, mediated in part by the mTOR pathway.

Transforming growth factor (TGF)-β has been associated with podocyte injury; we have examined its effect on podocyte bioenergetics. We studied transformed mouse podocytes, exposed to TGF-β1, using a label-free assay system, Seahorse XF24, which measures oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Both basal OCR and ATP generation-coupled OCR were significantly higher in podocytes exposed to 0.3–10 ng/ml of TGF-β1 for 24, 48, and 72 h. TGF-β1 (3 ng/ml) increased oxidative capacity 75%, and 96% relative to control after 48 and 72 h, respectively. ATP content was increased 19% and 30% relative to control after a 48- and 72-h exposure, respectively. Under conditions of maximal mitochondrial function, TGF-β1 increased palmitate-driven OCR by 49%. Thus, TGF-β1 increases mitochondrial oxygen consumption and ATP generation in the presence of diverse energy substrates. TGF-β1 did not increase cell number or mitochondrial DNA copy number but did increase mitochondrial membrane potential (MMP), which could explain the OCR increase. Reactive oxygen species (ROS) increased by 32% after TGF-β1 exposure for 48 h. TGF-β activated the mammalian target of rapamycin (mTOR) pathway, and rapamycin reduced the TGF-β1-stimulated increases in OCR, ECAR, ATP generation, cellular metabolic activity, and protein generation. Our data suggest that TGF-β1, acting, in part, via mTOR, increases mitochondrial MMP and OCR, resulting in increased ROS generation and that this may contribute to podocyte injury.

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NF-E2-Related Factor 2 Suppresses Intestinal Fibrosis by Inhibiting Reactive Oxygen Species-Dependent TGF-β1/SMADs Pathway

Digestive Diseases and Sciences ◽

10.1007/s10620-017-4710-z ◽

2017 ◽

Vol 63 (2) ◽

pp. 366-380 ◽

Cited By ~ 9

Author(s):

Yadi Guan ◽

Yue Tan ◽

Weiyu Liu ◽

Jun Yang ◽

Dongxu Wang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Related Factor ◽

Oxygen Species ◽

Intestinal Fibrosis ◽

Tgf Β1

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Cyclic stretch increases VEGF expression in pulmonary arterial smooth muscle cells via TGF-β1 and reactive oxygen species: a requirement for NAD(P)H oxidase

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00417.2004 ◽

2005 ◽

Vol 289 (2) ◽

pp. L288-L289 ◽

Cited By ~ 68

Author(s):

Eugenia Mata-Greenwood ◽

Albert Grobe ◽

Sanjiv Kumar ◽

Yelina Noskina ◽

Stephen M. Black

Keyword(s):

Reactive Oxygen Species ◽

Blood Flow ◽

Smooth Muscle ◽

Reactive Oxygen ◽

Cyclic Stretch ◽

Oxygen Species ◽

Vegf Expression ◽

Pulmonary Vessels ◽

Pulmonary Arterial ◽

Tgf Β1

Our previous studies have indicated that transforming growth factor (TGF)-β1 and VEGF expression are increased in the smooth muscle cell (SMC) layer of the pulmonary vessels of lambs with pulmonary hypertension secondary to increased pulmonary blood flow. Furthermore, we found that TGF-β1 expression increased before VEGF. Because of the increased blood flow in the shunt lambs, the SMC in the pulmonary vessels are exposed to increased levels of the mechanical force, cyclic stretch. Thus, in this study, using primary cultures of pulmonary arterial SMC isolated from pulmonary arteries of 4-wk-old lambs, we investigated the role of cyclic stretch in the apparent coordinated regulation of TGF-β1 and VEGF. Our results demonstrated that cyclic stretch induced a significant increase in VEGF expression both at the mRNA and protein levels ( P < 0.05). The increased VEGF mRNA was preceded by both an increased expression and secretion of TGF-β1 and an increase in reactive oxygen species (ROS) generation. In addition, a neutralizing antibody against TGF-β1 abolished the cyclic stretch-dependent increases in both superoxide generation and VEGF expression. Our data also demonstrated that cyclic stretch activated an NAD(P)H oxidase that was TGF-β1 dependent and that NAD(P)H oxidase inhibitors abolished the cyclic stretch-dependent increase in VEGF expression. Therefore, our results indicate that cyclic stretch upregulates VEGF expression via the TGF-β1-dependent activation of NAD(P)H oxidase and increased generation of ROS.

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TGF-β1 Triggers Oxidative Modifications and Enhances Apoptosis in Hit Cells Through Accumulation of Reactive Oxygen Species by Suppression of Catalase and Glutathione Peroxidase

Free Radical Biology and Medicine ◽

10.1016/s0891-5849(96)00493-5 ◽

1997 ◽

Vol 22 (6) ◽

pp. 1007-1017 ◽

Cited By ~ 75

Author(s):

Kazi N Islam ◽

Yoshiro Kayanoki ◽

Hideaki Kaneto ◽

Keiichiro Suzuki ◽

Michio Asahi ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Glutathione Peroxidase ◽

Reactive Oxygen ◽

Oxygen Species ◽

Oxidative Modifications ◽

Hit Cells ◽

Tgf Β1

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Modulation of Intracellular Reactive Oxygen Species Level in Chondrocytes by IGF-1, FGF, and TGF-β1

Connective Tissue Research ◽

10.1080/03008200701331516 ◽

2007 ◽

Vol 48 (3) ◽

pp. 149-158 ◽

Cited By ~ 25

Author(s):

Navid Jallali ◽

Hyder Ridha ◽

Christopher Thrasivoulou ◽

Peter Butler ◽

Timothy Cowen

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Intracellular Reactive Oxygen Species ◽

Species Level ◽

Reactive Oxygen Species Level ◽

Oxygen Species ◽

Tgf Β1

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Parathyroid hormone-related protein induces fibronectin up-regulation in rat mesangial cells through reactive oxygen species/Src/EGFR signaling

Bioscience Reports ◽

10.1042/bsr20182293 ◽

2019 ◽

Vol 39 (4) ◽

Author(s):

Hong-Min Chen ◽

Jia-Jia Dai ◽

Rui Zhu ◽

Fang-Fang Peng ◽

Su-Zhen Wu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Parathyroid Hormone ◽

Mesangial Cells ◽

Reactive Oxygen ◽

Oxygen Species ◽

Related Protein ◽

Egfr Signaling ◽

Mesenchymal Transition ◽

Parathyroid Hormone Related Protein ◽

Tgf Β1

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.

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