Resveratrol attenuates experimental allergic asthma in mice by restoring inositol polyphosphate 4 phosphatase (INPP4A)

Aich, Jyotirmoi; Mabalirajan, Ulaganathan; Ahmad, Tanveer; Khanna, Kritika; Rehman, Rakhshinda; Agrawal, Anurag; Ghosh, Balaram

doi:10.1016/j.intimp.2012.08.017

Cited by 46 publications

(36 citation statements)

References 36 publications

(44 reference statements)

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“…Treatment of asthmatic mice with a natural dietary antioxidant, Resveratrol, alleviated asthmatic features, associated with inhibited calpain activation and restored expression of INPP4A in bronchial epithelia [37].…”

Section: Inpp4a Is a Suppressor Of Asthmamentioning

confidence: 97%

Phosphatidylinositol (3,4) bisphosphate-specific phosphatases and effector proteins: A distinct branch of PI3K signaling

Marshall

2015

Cellular Signalling

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Section: Inpp4a Is a Suppressor Of Asthmamentioning

confidence: 97%

Phosphatidylinositol (3,4) bisphosphate-specific phosphatases and effector proteins: A distinct branch of PI3K signaling

Marshall

2015

Cellular Signalling

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“…11) Several other studies have also confirmed that resveratrol exerts anti-asthmatic effects 12,13) ; however, the mechanisms underlying resveratrol activity in the treatment of asthma have not been clearly elucidated, including whether the inhibition of airway inflammation by resveratrol occurs via the regulation of PTEN expression. In addition to the presence of inflammatory cells, airway remodeling and smooth muscle hyperplasia are important and cardinal features of asthma.…”

mentioning

confidence: 99%

Antiasthmatic Effects of Resveratrol in Ovalbumin-Induced Asthma Model Mice Involved in the Upregulation of PTEN

Chen

Tang

et al. 2015

Biological & Pharmaceutical Bulletin

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Resveratrol, a natural polyphenolic compound known for its antioxidative and antiinflammatory effects, exerts antiasthmatic effects, although the mechanism underlying these effects remains elusive. The phosphatase and tensin homology deleted on chromosome ten gene (PTEN) is involved in the pathogenesis of asthma, and PTEN overexpression in asthmatic mice improved asthma symptoms. To investigate whether the antiasthmatic mechanisms of resveratrol correlated with the upregulation of PTEN expression, an ovalbumin (OVA)-induced murine asthma model was used to determine the effectiveness of resveratrol treatment. PTEN mRNA and protein expression was assessed with real-time polymerase chain reaction (PCR) and immunochemistry. To determine whether airway remodeling occurred, the inner airway wall, mucous layer, and smooth muscle areas were each determined using an image analysis system. The lung epithelial cell line 16HBE was used to study the regulation of PTEN expression levels by resveratrol in vitro. Our data demonstrated that resveratrol inhibited OVA-induced airway inflammation and airway remodeling in asthmatic mice. PTEN expression was decreased in the murine asthma model, although the expression of PTEN was restored following treatment with resveratrol. Correlation efficiency analysis showed that PTEN expression was associated with the degree of airway remodeling. Further in vitro studies demonstrated that the inhibition of Sirtuin 1 (SIRT1) activity by a SIRT1 inhibitor and RNA interference decreased PTEN protein expression, while resveratrol attenuated the decreases in PTEN expression induced by the SIRT1 inhibitor. These data suggest the mechanism of the antiasthmatic effects of resveratrol in an OVA-induced murine asthma model, which resulted in the upregulation of PTEN via SIRT1 activation.Key words resveratrol; asthma; phosphatase and tensin homology deleted on chromosome ten; Sirtuin 1 (SIRT1) Asthma is an inflammatory disease that has been verified in clinical practice. Corticosteroids are unique anti-inflammatory agents and represent an important therapy for controlling asthma symptoms.

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“…INPP4A negatively regulates the levels of PI(3,4)P2, an AKT activator like PI(3,4,5)P3, by removing the phosphate of PI(3,4)P2 to yield PI(3)P. INPP4A knockout sustained AKT activation and thereby promoted mouse embryonic fibroblast proliferation, survival, and tumorigenesis [18, 38]. It has been noted that INPP5J suppresses PI3K/AKT signaling by reducing AKT at its hydrophobic motif site, Ser473, and was recently found to be downregulated in melanoma and esophageal squamous cell carcinoma, leading to the promotion of cell proliferation and tumorigenicity in vivo [19, 39].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular carcinoma by disrupting of PI3K/AKT negative regulation

et al. 2015

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Recent studies have shown that multiple phosphatases deactivate the PI3K/AKT signaling pathway. Here we demonstrated that, by suppressing multiple phosphatases, miR-3127 promotes growth of hepatocellular carcinoma (HCC). Our study also reveals clinical significance of miR-3127 expression in HCC patients. MiR-3127 expression was markedly upregulated in HCC tissues and cells. Furthermore, high miR-3127 expression was associated with an aggressive phenotype and poor prognosis. MiR-3127 overexpression promoted HCC cell proliferation in vitro and tumor growth in vivo. Also, miR-3127 accelerated G1-S transition by activating AKT/FOXO1 signaling, by directly targeting the 3′ untranslated regions (3`UTR) of pleckstrin homology domain leucine-rich repeat protein phosphatase 1/2 (PHLPP1/2), inositol polyphosphate phosphatase 4A (INPP4A), and inositol polyphosphate-5-phosphatase J (INPP5J) mRNA, repressing their expression. In agreement, the miRNA antagonist antagomir-3127 suppressed HCC cell proliferation and tumor growth by inhibiting the AKT/FOXO1 signaling. Taken together, these findings suggest that silencing miR-3127 might be a potential therapeutic strategy.

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Resveratrol attenuates experimental allergic asthma in mice by restoring inositol polyphosphate 4 phosphatase (INPP4A)

Cited by 46 publications

References 36 publications

Phosphatidylinositol (3,4) bisphosphate-specific phosphatases and effector proteins: A distinct branch of PI3K signaling

Phosphatidylinositol (3,4) bisphosphate-specific phosphatases and effector proteins: A distinct branch of PI3K signaling

Antiasthmatic Effects of Resveratrol in Ovalbumin-Induced Asthma Model Mice Involved in the Upregulation of PTEN

MicroRNA-3127 promotes cell proliferation and tumorigenicity in hepatocellular carcinoma by disrupting of PI3K/AKT negative regulation

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