Osteopontin modulates angiotensin II–induced inflammation, oxidative stress, and fibrosis of the kidney

Wolak, Talya; Kim, Hyun-Ju; Ren, Yi; Kim, Jason; Vaziri, Nosratola D.; Nicholas, Susanne B.

doi:10.1038/ki.2009.90

Cited by 103 publications

(78 citation statements)

References 63 publications

(76 reference statements)

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“…118,119 In addition, through thrombospondin 1, Ang II activates the release of active TGF␤ from the latent complex. 118,119 Finally, Ang II directly upregulates type 2 TGF␤ receptors by mediating transcriptional activity of the receptor gene. 36 tiation from tubular cells to macula densa cells can be controlled by angiotensin type 2 receptors (AT2Rs).…”

Section: Ang II and Epithelial-mesenchymal Transitionmentioning

confidence: 99%

“…118,119 In several models of kidney fibrosis with increases in local Ang II, endothelin simultaneously increases endothelin-1 (ET-1). 85,89 In a model of severe Ang II-dependent hypertension in Ren-2 transgenic rats, the role of Ang II, ET-1, and L-type calcium channels in the development of glomerular, vascular, and tubulointerstitial fibrosis is observed after treatment with irbesartan, bosentan, and a selective endothelin receptor antagonist.…”

Section: Ang II and Other Profibrotic Factorsmentioning

confidence: 99%

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Angiotensin II as a Morphogenic Cytokine Stimulating Renal Fibrogenesis

Rüster

Wolf

2011

Journal of the American Society of Nephrology

171

150

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Chronic kidney disease (CKD) is increasing worldwide. Although the cause of its progression is multifactorial, 1-3 activation of the renin-angiotensin-aldosterone system (RAAS) is a key effector and RAAS inhibitors are among the beststudied renoprotective agents. 4 -7 Although the RAAS is complex, with new peptides such as angiotensin 1-7 and angiotensin IV exhibiting profibrotic effects by binding to specific receptors as well as observations that aldosterone and even renin itself can stimulate fibrogenesis in the kidney, 8 -12 and angiotensin II (Ang II) blockade can stimulate renin release, 13 the review presented here focuses exclusively on Ang II as the major component of the RAAS effect on morphogenesis. There are several excellent reviews covering the other components of the RAAS and their profibrotic actions in the kidney. 8 -10,14 The classic view of Ang II as a vasoactive agent involved in local and systemic hemodynamic regulation 15 needs extension to encompass its properties as a morphogenic cytokine with an active role in renal pathology. 16,17 Ang II was first described 2 decades ago as stimulating the hypertrophy of tubular cells and the associated increase in collagen secretion. 18,19 Fibrosis is the final common pathway leading to renal diseases of diverse etiology, including inflammation, hemodynamics, and metabolic injury. 20 -22 Ang II modulates renal cell growth and extracellular matrix (ECM) synthesis or degradation. 17,[23][24][25] For example, overexpression of renin and angiotensinogen in rat glomeruli leads to expanded ECM without inducing systemic hypertension. 26,27 The stimulatory effects of Ang II on increased collagen expression depend on various mechanisms. In addition to angiotensin-converting enzyme (ACE), which is the most well known enzyme capable of Ang II formation, other non-ACE Ang II-generating pathways are currently under study. 28 ACE inhibitors also diminish cellular infiltrates and inflammatory markers in many models of renal injury. 29 ANG II AND TGF␤The interactions between Ang II and the TGF␤ axis are multiple and complex (Figure 1). 29 -31 TGF␤ is a fibrogenic and anti-inflammatory cytokine and plays a critical role in the pathophysiology of renal injury. 32,33 Ang II stimulates transcription and synthesis of TGF␤, particularly TGF␤1, in cultured murine proximal tubular cells and also upregulates specific receptors for TGF␤, further enhancing its profibrogenic action. 34 -36 Ang II directly stimulates complex interactions in the ABSTRACTInhibitors of the renin-angiotensin-aldosterone system attenuate glomerulosclerosis and interstitial fibrosis. Although the mechanisms underlying their antifibrotic effects are complex, angiotensin II (Ang II) emerges as a major profibrogenic cytokine. Ang II modulates renal cell growth, extracellular matrix synthesis, and degradation by multiple fibrotic pathways. One of the main targets of Ang II in renal fibrosis is TGF␤. Many, but not all, of the stimulatory effects of Ang II on fibrogenesis depend on the induction...

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Section: Ang II and Epithelial-mesenchymal Transitionmentioning

confidence: 99%

Section: Ang II and Other Profibrotic Factorsmentioning

confidence: 99%

Angiotensin II as a Morphogenic Cytokine Stimulating Renal Fibrogenesis

Rüster

Wolf

2011

Journal of the American Society of Nephrology

171

150

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“…Recently, Ang II was used to induce the differentiation of bmMSCs to other functional cell lineages, such as cardiomyocytes, adipocytes and smooth muscle-like cells (4)(5)(6). It was demonstrated that Ang II induces inflammatory responses in vitro in several types of cells, including endothelial cells, smooth muscle cells, fibroblasts and kidney tubule epithelial cells (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Aspirin attenuates angiotensin II-induced inflammation in bone marrow mesenchymal stem cells via the inhibition of ERK1/2 and NF-κB activation

Zhang

Wang

et al. 2013

Biomedical Reports

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Abstract. Angiotensin II (Ang II) is a peptide hormone that plays a critical role in numerous physiological and pathophysiological processes. It is also commonly used as an inducer for the directional differentiation of bone marrow mesenchymal stem cells (bmMSCs). Previous studies demonstrated that Ang II induces inflammatory responses in endothelial cells, smooth muscle cells and fibroblasts. Aspirin is generally used as analgesic, antipyretic and occasionally anti-inflammatory medication. Whether aspirin suppresses inflammatory responses in bmMSCs has not been elucidated. In this study, we investigated the effect of aspirin on Ang II-induced inflammation in bmMSCs. Our results demonstrated that Ang II (10 nM-10 µM) increased the secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-6 from bmMSCs in a dose-dependent manner. This result was further confirmed by a reverse transcription-polymerase chain reaction (RT-PCR) assay, which demonstrated a dose-dependent increase in the mRNA expression of TNF-α, IL-6, IL-1β and monocyte chemotactic protein-1 (MCP-1) in bmMSCs following exposure to Ang II. Furthermore, it was also observed that Ang II increased the expression of phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) and phospho-nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB)-p65 in bmMSCs. The application of aspirin (0.1 mM) significantly inhibited the activation of ERK1/2 and NF-κB, the expression of TNF-α, IL-6, IL-1β and MCP-1 genes and the secretion of TNF-α and IL-6. Our findings indicated that aspirin may attenuate Ang II-induced inflammation in bmMSCs via the inhibition of ERK1/2 and NF-κB activation.

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“…In the literature, there are reports suggesting that this protein participates in the pathogenesis of SSc. OPN has a chemotactic and pro-ibrotic properties [77,78]. Moreover, enhances the pro-inlammatory Th1 cell response, which is believed to be crucial in SSc pathogenesis.…”

Section: Systemic Sclerosismentioning

confidence: 99%

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

Kaleta¹

2017

Genetic Polymorphisms

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Osteopontin (OPN) is a pleiotropic protein, important in bone remodeling and immune system signaling. OPN is synthesized in a variety of cells and tissues. It can be found not only in bone cells but also in immune cells (B and T lymphocytes, natural killer (NK) cells, natural killer T (NKT) cells, macrophages, neutrophils, and dendritic cells). OPN regulates T-helper 1/T-helper 2 (Th1/Th2) balance, stimulates B cells to antibodies production, regulates macrophages and neutrophils function, and activates dendritic cells. A number of factors, including hormones, cytokines, and polymorphisms of promoter region of OPN gene, regulate protein expression. OPN and variants of the OPN gene have been associated with the pathogenesis of multiple disorders, including systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, systemic sclerosis, inlammatory bowel diseases, asthma, type 1 diabetes, and many other. However, some studies gave diferent or inconclusive results. Thus, the role of OPN polymorphic variants in autoimmune diseases needs to be beter deined and explored as a diagnostic and therapeutic target to monitor and treat immune-mediated conditions.

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Osteopontin modulates angiotensin II–induced inflammation, oxidative stress, and fibrosis of the kidney

Cited by 103 publications

References 63 publications

Angiotensin II as a Morphogenic Cytokine Stimulating Renal Fibrogenesis

Angiotensin II as a Morphogenic Cytokine Stimulating Renal Fibrogenesis

Aspirin attenuates angiotensin II-induced inflammation in bone marrow mesenchymal stem cells via the inhibition of ERK1/2 and NF-κB activation

Osteopontin (OPN) Gene Polymorphisms and Autoimmune Diseases

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