RETRACTED ARTICLE: PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial–mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis

Li, Guoqing; Zhang, Yu; Liú, Dan; Qian, Yayun; Zhang, Hua; Guo, Shiyu; Sunagawa, Makoto; Hisamitsu, Tadashi; Liu, Yanqing

doi:10.1007/s11010-012-1463-z

Cited by 79 publications

(59 citation statements)

References 34 publications

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“…Accumulating evidences have shown that PI3K/AKT pathway activates HIF-1 α in various disease models40, 41. Moreover, studies demonstrated that MAPK/ERK1 pathway also involved in activation of HIF-1 α42-44.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

Xu¹,

Li²,

Zhang³

et al. 2016

Int. J. Med. Sci.

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Resveratrol, a plant-derived polyphenolic compound and a phytoestrogen, was shown to possess multiple protective effects including anti-inflammatory response and anti-oxidative stress. Hypoxic pulmonary hypertension (HPH) is a progressive disease characterized by sustained vascular resistance and marked pulmonary vascular remodeling. The exact mechanisms of HPH are still unclear, but inflammatory response and oxidative stress was demonstrated to participate in the progression of HPH. The present study was designed to investigate the effects of resveratrol on HPH development. Sprague-Dawley rats were challenged by hypoxia exposure for 28 days to mimic hypoxic pulmonary hypertension along with treating resveratrol (40 mg/kg/day). Hemodynamic and pulmonary pathomorphology data were then obtained, and the anti-proliferation effect of resveratrol was determined by in vitro assays. The anti-inflammation and anti-oxidative effects of resveratrol were investigated in vivo and in vitro. The present study showed that resveratrol treatment alleviated right ventricular systolic pressure and pulmonary arterial remodeling induced by hypoxia. In vitro experiments showed that resveratrol notably inhibited proliferation of pulmonary arterial smooth muscle cells in an ER-independent manner. Data showed that resveratrol administration inhibited HIF-1 α expression in vivo and in vitro, suppressed inflammatory cells infiltration around the pulmonary arteries, and decreased ROS production induced by hypoxia in PAMSCs. The inflammatory cytokines' mRNA levels of tumor necrosis factor α, interleukin 6, and interleukin 1β were all suppressed by resveratrol treatment. The in vitro assays showed that resveratrol inhibited the expression of HIF-1 α via suppressing the MAPK/ERK1 and PI3K/AKT pathways. The antioxidant axis of Nuclear factor erythroid-2 related factor 2/ Thioredoxin 1 (Nrf-2/Trx-1) was up-regulated both in lung tissues and in cultured PASMCs. In general, the current study demonstrated that resveratrol may prevent pulmonary hypertension through its anti-proliferation, anti-inflammation and antioxidant effects. Hence, the present data may offer novel targets and promising pharmacological perspective for treating hypoxic pulmonary hypertension.

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Section: Discussionmentioning

confidence: 99%

Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

Xu¹,

Li²,

Zhang³

et al. 2016

Int. J. Med. Sci.

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show abstract

“…Notch-1 intracellular domain (Notch-1), Janus kinase/signal transducers and activators of transcription (JAK-STAT) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) in synovial tissue and cells [13][14][15][16]. Evidence of a key role for metabolism in the regulation of synovial inflammation has recently emerged, where proliferation and rapid activation of immune and stromal cells requires a switch in cell metabolism from a resting regulatory state to a highly metabolically active state, in order to maintain energy homeostasis [6,17].…”

Section: Review Series: Translating Immunometabolismmentioning

confidence: 99%

Section: Review Series: Translating Immunometabolismmentioning

confidence: 99%

Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis

Fearon

Hanlon

Wade

et al. 2018

Clinical and Experimental Immunology

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Rheumatoid arthritis is characterized by synovial proliferation, neovascularization and leucocyte extravasation leading to joint destruction and functional disability. The blood vessels in the inflamed synovium are highly dysregulated, resulting in poor delivery of oxygen; this, along with the increased metabolic demand of infiltrating immune cells and inflamed resident cells, results in the lack of key nutrients at the site of inflammation. In these adverse conditions synovial cells must adapt to generate sufficient energy to support their proliferation and activation status, and thus switch their cell metabolism from a resting regulatory state to a highly metabolically active state. This alters redox-sensitive signalling pathways and also results in the accumulation of metabolic intermediates which, in turn, can act as signalling molecules that further exacerbate the inflammatory response. The RA synovium is a multi-cellular tissue, and while many cell types interact to promote the inflammatory response, their metabolic requirements differ. Thus, understanding the complex interplay between hypoxia-induced signalling pathways, metabolic pathways and the inflammatory response will provide better insight into the underlying mechanisms of disease pathogenesis. OTHER ARTICLES PUBLISHED IN THIS REVIEW SERIESTranslating immunometabolism: towards curing human diseases by targeting metabolic processes underpinning the immune response. Clinical and Experimental Immunology 2019, 197: 141-142. T cell metabolism in chronic viral infection. Clinical and Experimental Immunology 2019, 197: 143-152. Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting. Clinical and Experimental Immunology 2019, 197: 153-160. Sensing between reactions -how the metabolic microenvironment shapes immunity.

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“…Conditional knockout of HIF-1α in myeloid cells in a murine model of RA significantly reduced synovial inflammation and disease progression (57). Similarly, HIF-1α played a critical role in hypoxia-induced synovial hyperplasia and inflammatory cell infiltration in murine collagen-induced arthritis (58). HIF also induces expression of inflammatory cytokines including IL-6, IL-8, TNF-α, and IL-1β in rheumatoid synovial fibroblasts (59).…”

Section: Pathological Functions Of Angptl4 In Ramentioning

confidence: 99%

Multiple Roles of Angiopoietin-Like 4 in Osteolytic Disease

Knowles

2017

Front. Endocrinol.

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Hypoxia and the hypoxia-inducible factor (HIF) transcription factor drive pathological bone loss in conditions including rheumatoid arthritis (RA), osteoarthritis, osteoporosis, primary bone tumours, and bone metastatic cancer. There is therefore considerable interest in determining the function(s) of HIF-induced genes in these pathologies. Angiopoietin-like 4 (ANGPTL4) is an adipose-derived, HIF-1α- and PPARγ-induced gene that was originally discovered as an endocrine and autocrine/paracrine regulator of lipid metabolism. Given the inverse relationship between bone adiposity and fracture risk, ANGPTL4 might be considered a good candidate for mediating the downstream effects of HIF-1α relevant to osteolytic disease. This review will consider the possible roles of ANGPTL4 in regulation of osteoclast-mediated bone resorption, cartilage degradation, angiogenesis, and inflammation, focusing on results obtained in the study of RA. Possible roles in other musculoskeletal pathologies will also be discussed. This will highlight ANGPTL4 as a regulator of multiple disease processes, which could represent a novel therapeutic target in osteolytic musculoskeletal disease.

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RETRACTED ARTICLE: PI3 kinase/Akt/HIF-1α pathway is associated with hypoxia-induced epithelial–mesenchymal transition in fibroblast-like synoviocytes of rheumatoid arthritis

Cited by 79 publications

References 34 publications

Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

Resveratrol alleviate hypoxic pulmonary hypertension via anti-inflammation and anti-oxidant pathways in rats

Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis

Multiple Roles of Angiopoietin-Like 4 in Osteolytic Disease

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