Transforming growth factor-β1 regulated phosphorylated AKT and interferon gamma expressions are associated with epithelial cell survival in rhesus macaque colon explants

Pahar, Bapi; Pan, Diganta; Lala, Wendy; Kenway-Lynch, Carys S.; Das, Arpita

doi:10.1016/j.clim.2015.03.001

Cited by 9 publications

(17 citation statements)

References 50 publications

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“…Akt, which acts downstream of the phosphatidylinositol 3-kinase (PI3K), regulates cell survival mechanisms and can be activated by various growth factors, including insulin, the insulin-like growth factor, and the epithelial growth factor. The activation of Akt requires the phosphorylation of both thr308/309 on its kinase activation ring and ser473/474 on its carboxyl terminus [ 21 ]. Once activated, p-Akt is a powerful driver for cell survival and can counteract or inactivate intermediate components of the apoptosis cascades, such as the proapoptotic factors BAD and caspase-9, and members of the forkhead transcription factor family [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer

Jin

Yuan

et al. 2019

Biochemistry and Biophysics Reports

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Brain metastasis (BM) of non-small cell lung cancer (NSCLC) is relatively common and has a poor prognosis. Moreover, identifying which patients are more likely to develop BM is challenging. Akt, a serine/threonine-specific protein kinase, can be activated in various tumors, including lung cancer, and may be associated with poor prognosis. Here, we used immunohistochemistry to evaluate phosphorylated-Akt (p-Akt) expression in tumor tissues of 99 NSCLC patients. We also analyzed the genotype of the patients for two single nucleotide polymorphisms (SNPs) of the AKT1 gene, rs2498804 and rs2494732. We found that p-Akt expression differs between NSCLC patients and correlates with the risk of BM. Indeed, patients exhibiting medium to high p-Akt expression had a higher incidence of BM than those exhibiting low to no p-Akt expression (39% vs 16%). Our data also show that patients with the rs2498804 GT/GG and rs2494732 CT/TT variant genotypes were more likely to exhibit higher levels of p-Akt expression than those with the rs2498804 TT and rs2494732 CC variant genotypes (35% vs. 24% and 37% vs. 25%, respectively). Our results suggest that the level of expression of p-Akt, which may be affected by the AKT1 genotype, is correlated with the risk of BM. However, further studies are needed to establish p-Akt as a predictive marker for BM in NSCLC patients.

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Section: Discussionmentioning

confidence: 99%

Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer

Jin

Yuan

et al. 2019

Biochemistry and Biophysics Reports

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“…After staining, slides were washed, and labeled tissue sections were mounted using Prolong Gold antifade medium (Life Technologies) and imaged using a TCS SP2 confocal laser scanning microscope (Leica, Wetzlar, Germany) . Negative control slides were incorporated in each experiment either by omitting the primary antibody or using isotype IgG1 and IgG (H+L) controls . The midbrain contained multiple multinucleated giant cells (MNGC) infected with SIV with occasional CD3+ T cells around these MNGC (Fig.…”

Section: Quantification Of Total Ki67pos and Siv Rna‐positive Prolifementioning

confidence: 99%

“…The macaque maintained a high plasma viral load (log 10 6.6 RNA copies/ ml of plasma using bDNA assay from Siemens with detection limit of 125 copies/mL of plasma) and low peripheral blood CD4 counts (below Germany). [14][15][16][17] Negative control slides were incorporated in each experiment either by omitting the primary antibody or using isotype IgG1 and IgG (H+L) controls. [14][15][16] The midbrain contained multiple multinucleated giant cells (MNGC) infected with SIV with occasional CD3+ T cells around these MNGC (Fig.…”

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confidence: 99%

A significant productive in vivo infection of resting cells with simian immunodeficiency virus in a macaque with AIDS

Pahar

Lala

Kuebler

et al. 2017

J of Medical Primatology

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Identifying the cells that can be infected with HIV in vivo, and thus potentially persist as latent reservoirs is of high priority. Here, we report the major infected cells in a chronically-SIV infected macaque that developed AIDS and encephalitis. Majority of the infected cells were detected as non-proliferating resting cells. SIV infected non-proliferating resting cells were found to be playing an important role in viral pathogenesis, persistence or reservoir formation.

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“…Transforming growth factor-β1 (TGF-β1) is an immunoregulatory cytokine that is produced by a variety of immune cells including lymphocytes, macrophages, dendritic cells, and intestinal epithelial cells. It has pleiotropic effects on cell migration, differentiation, proliferation, and survival, and is also involved in regulating immune responses [ 1 , 2 ]. Highlighting its role in maintaining intestinal homeostasis and epithelial cell integrity, we have recently demonstrated that TGF-β promotes epithelial cell survival in rhesus macaque (RhM) colon explants via increased pAKT and decreased IFNγ expression [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Intestinal TGF-β/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques

Boby

Ransom

Pace

et al. 2021

Cells

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Transforming growth factor-β signaling (TGF-β) maintains a balanced physiological function including cell growth, differentiation, and proliferation and regulation of immune system by modulating either SMAD2/3 and SMAD7 (SMAD-dependent) or SMAD-independent signaling pathways under normal conditions. Increased production of TGF-β promotes immunosuppression in Human Immunodeficiency Virus (HIV)/Simian Immunodeficiency Virus (SIV) infection. However, the cellular source and downstream events of increased TGF-β production that attributes to its pathological manifestations remain unknown. Here, we have shown increased production of TGF-β in a majority of intestinal CD3−CD20−CD68+ cells from acute and chronically SIV infected rhesus macaques, which negatively correlated with the frequency of jejunum CD4+ T cells. No significant changes in intestinal TGF-β receptor II expression were observed but increased production of the pSMAD2/3 protein and SMAD3 gene expression in jejunum tissues that were accompanied by a downregulation of SMAD7 protein and gene expression. Enhanced TGF-β production by intestinal CD3−CD20−CD68+ cells and increased TGF-β/SMAD-dependent signaling might be due to a disruption of a negative feedback loop mediated by SMAD7. This suggests that SIV infection impacts the SMAD-dependent signaling pathway of TGF-β and provides a potential framework for further study to understand the role of viral factor(s) in modulating TGF-β production and downregulating SMAD7 expression in SIV. Regulation of mucosal TGF-β expression by therapeutic TGF-β blockers may help to create effective antiviral mucosal immune responses.

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Transforming growth factor-β1 regulated phosphorylated AKT and interferon gamma expressions are associated with epithelial cell survival in rhesus macaque colon explants

Cited by 9 publications

References 50 publications

Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer

Phosphorylated-Akt overexpression is associated with a higher risk of brain metastasis in patients with non-small cell lung cancer

A significant productive in vivo infection of resting cells with simian immunodeficiency virus in a macaque with AIDS

Enhanced Intestinal TGF-β/SMAD-Dependent Signaling in Simian Immunodeficiency Virus Infected Rhesus Macaques

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