Angiotensin II induces thrombospondin-1 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF-β<sub>1</sub>

Naitô, Takayuki; Takao, Masaki; Nikolic‐Paterson, David J.; Tanji, Chie; Yorioka, Noriaki; Kohno, Nobuoki

doi:10.1152/ajprenal.00139.2003

Cited by 138 publications

(105 citation statements)

References 41 publications

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“…These data suggest that a pathway or pathways other than PI3K-AKT regulate TSP-1 expression. Delayed activation of p38 mitogen-activated protein kinases (MAPK) has been reported to regulate TSP-1 expression in other cancer cell types (Takekawa et al, 2002;Naito et al, 2004). Early activation of p38 kinase by the anti-HER2 antibody ID5 was reported previously (Le et al, 2000).…”

Section: Resultsmentioning

confidence: 80%

“…In other cell systems, delayed activation of the p38 MAP kinase pathway also has a negative impact on cell proliferation by inducing apoptosis (Daly et al, 1999;Takekawa et al, 2002;Bulavin and Fornace, 2004;Naito et al, 2004). Treatment of BT474 and SKBr3 cells with anti-HER2 antibodies for 72 h does not induce significant apoptosis (Le et al, 2003(Le et al, , 2005a.…”

Section: Discussionmentioning

confidence: 99%

“…The signaling pathways that regulate TSP-1 expression also remain controversial. MAP kinase signaling, including the activation of p38 and JNK, has been shown to regulate TSP-1 expression (Takekawa et al, 2002;Naito et al, 2004), as has the PI3K pathway (Watnick et al, 2003). HER2 signaling can affect TSP-1 expression in breast cancer.…”

Section: Introductionmentioning

confidence: 99%

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HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

et al. 2006

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We determined the impact of HER2 signaling on two proangiogenic factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), and on an antiangiogenic factor, thrombospondin-1 (TSP-1). Re-expression of HER2 in MCF-7 and T-47D breast cancer cells that endogenously express low levels of HER2 resulted in elevated expression of VEGF and IL-8 and decreased expression of TSP-1. Inhibition of HER2 with a humanized anti-HER2 antibody (trastuzumab, or Herceptin s ) or a retrovirus-mediated small interfering RNA against HER2 (siHER2) decreased VEGF and IL-8 expression, but increased TSP-1 expression in BT474 breast cancer cells that express high levels of HER2. These in vitro results were further evaluated by treatment of BT474 xenografts in immunosuppressed mice with trastuzumab. Trastuzumab inhibited growth of BT474 xenografts and decreased microvascular density associated with downregulation of VEGF and IL-8 and with upregulation of TSP-1 expression. Inhibiting the PI3K-AKT pathway decreased VEGF and IL-8 expression. AKT1 overexpession increased VEGF and IL-8 expression, but did not increase TSP-1 expression. A p38 kinase inhibitor, SB203580, instead blocked TSP-1 expression and a p38 activator, MKK6, increased TSP-1 expression. Trastuzumab stimulated sustained p38 activation and SB203580 attenuated the TSP-1 upregulation induced by trastuzumab. HER2 signaling therefore influences the equilibrium between pro-and antiangiogenic factors via distinct signaling pathways. Trastuzumab inhibits angiogenesis and tumor growth, at least in part, through activation of the HER2-p38-TSP-1 pathway and inhibition of the HER2-PI3K-AKT-VEGF/IL-8 pathway.

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Section: Resultsmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

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HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

et al. 2006

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“…MAPKs are pivotal mediators of the effects of Ang II on tissue structure by increasing TGF‐β1 expression, leading to atrial fibrosis 38, 39, 40. TGF‐β1 is a cytokine that regulates cell proliferation, apoptosis, migration, and synthesis of ECM, such as fibronectin and collagen in the atrium 41, 42.…”

Section: Discussionmentioning

confidence: 99%

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

Yang

Zhao

Qiu

et al. 2018

JAHA

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BackgroundThere are several mechanisms, including inflammation, oxidative stress and abnormal calcium homeostasis, involved in the pathogenesis of atrial fibrillation. In diabetes mellitus (DM), increased oxidative stress may be attributable to higher xanthine oxidase activity. In this study, we examined the relationship between oxidative stress and atrial electrical and structural remodeling, and calcium handling abnormalities, and the potential beneficial effects of the xanthine oxidase inhibitor allopurinol upon these pathological changes.Methods and ResultsNinety rabbits were randomly and equally divided into 3 groups: control, DM, and allopurinol‐treated DM group. Echocardiographic and hemodynamic assessments were performed in vivo. Serum and tissue markers of oxidative stress and atrial fibrosis, including the protein expression were examined. Atrial interstitial fibrosis was evaluated by Masson trichrome staining. ICaL was measured from isolated left atrial cardiomyocytes using voltage‐clamp techniques. Confocal microscopy was used to detect intracellular calcium transients. The Ca2+ handling protein expression was analyzed by Western blotting. Mitochondrial‐related proteins were analyzed as markers of mitochondrial function. Compared with the control group, rabbits with DM showed left ventricular hypertrophy, increased atrial interstitial fibrosis, oxidative stress and fibrosis markers, ICaL and intracellular calcium transient, and atrial fibrillation inducibility. These abnormalities were alleviated by allopurinol treatment.ConclusionsAllopurinol, via its antioxidant effects, reduces atrial mechanical, structural, ion channel remodeling and mitochondrial synthesis abnormalities induced by DM‐related increases in oxidative stress.

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“…Although several studies have shown that antagonism of angiotensin II signaling results in decreased TGF-b signaling in a variety of tissues, including kidney, lung, skeletal muscle, heart, and aorta (Shihab et al 1997;Sun et al 1998;Lavoie et al 2005;Habashi et al 2006;Yao et al 2006;Cohn et al 2007;Podowski et al 2012), the exact mechanism by which this occurs is not fully understood (Gibbons et al 1992;Stouffer and Owens 1992;Wolf et al 1993Wolf et al , 1999Kagami et al 1994;Lee et al 1995;Campbell and Katwa 1997;Fukuda et al 2000;Boffa et al 2003;Naito et al 2004;RodriguezVita et al 2005;Zhou et al 2006;Chen et al 2013). Suppression of excessive Erk1 and Erk2 MAPK activation with losartan or an inhibitor of MAPK kinase (MAPKK, also known as MEK) has been shown to normalize aortic architecture and aneurysm pathology in MFS mouse models (Habashi et al 2011), indicating that Erk MAPK activation is critical to aneurysm progression.…”

Section: Tgf-b Family Signaling In Connective Tissuesmentioning

confidence: 99%

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

MacFarlane

Haupt

Dietz

et al. 2017

Cold Spring Harb Perspect Biol

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The transforming growth factor b (TGF-b) family of signaling molecules, which includes TGF-bs, activins, inhibins, and numerous bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs), has important functions in all cells and tissues, including soft connective tissues and the skeleton. Specific TGF-b family members play different roles in these tissues, and their activities are often balanced with those of other TGF-b family members and by interactions with other signaling pathways. Perturbations in TGF-b family pathways are associated with numerous human diseases with prominent involvement of the skeletal and cardiovascular systems. This review focuses on the role of this family of signaling molecules in the pathologies of connective tissues that manifest in rare genetic syndromes (e.g., syndromic presentations of thoracic aortic aneurysm), as well as in more common disorders (e.g., osteoarthritis and osteoporosis). Many of these diseases are caused by or result in pathological alterations of the complex relationship between the TGF-b family of signaling mediators and the extracellular matrix in connective tissues.T he transforming growth factor b (TGF-b) family of cytokines comprises the three TGF-b proteins (TGF-b1, TGF-b2, and TGFb3) and related growth and differentiation factors such as activins, inhibins, bone morphogenic proteins (BMPs), and growth and differentiation factors (GDFs). These molecules play critical roles both in normal development and in several pathological conditions, including inflammation, fibrosis, and cancer (reviewed in Li and Flavell 2006;Gordon and Blobe 2008;Ikushima and Miyazono 2010). This review focuses on the role of these proteins in development and homeostasis of the skeleton and other connective tissues (summarized in Fig. 1) and on the diseases that ensue when these pathways are altered. Aberrant signaling in these pathways has been associated with common connective 6 These authors contributed equally to this work.

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Angiotensin II induces thrombospondin-1 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF-β₁

Cited by 138 publications

References 41 publications

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

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Angiotensin II induces thrombospondin-1 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF-β1

Cited by 138 publications

References 41 publications

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

HER2 signaling modulates the equilibrium between pro- and antiangiogenic factors via distinct pathways: implications for HER2-targeted antibody therapy

Xanthine Oxidase Inhibitor Allopurinol Prevents Oxidative Stress‐Mediated Atrial Remodeling in Alloxan‐Induced Diabetes Mellitus Rabbits

TGF-β Family Signaling in Connective Tissue and Skeletal Diseases

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Angiotensin II induces thrombospondin-1 production in human mesangial cells via p38 MAPK and JNK: a mechanism for activation of latent TGF-β₁