IFN-γ Contributes to the Immune Mechanisms of Hypertension

Benson, Lance N.; Liu, Yunmeng; Deck, Katherine; Mora, Christoph; Mu, Shengyu

doi:10.34067/kid.0001292022

Cited by 15 publications

(13 citation statements)

References 121 publications

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“…Based on its role in the immune system, the expression level of this gene can affect the immune response. Another gene optimized here that has a role in the immune system is the IFNG ( IFN-γ ) gene [25][26]. The other selected gene is TNF or TNF-α , which is believed to have pathogenetic and therapeutic applications [27].…”

Section: Resultsmentioning

confidence: 99%

UTRGAN: Learning to Generate 5’ UTR Sequences for Optimized Translation Efficiency and Gene Expression

Barazandeh

Furkan

Hincer

et al. 2023

Preprint

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The 5′ untranslated region (5′ UTR) of the messenger RNA plays a crucial role in the translatability and stability of a molecule. Thus, it is an important component in the design of synthetic biological circuits for high and stable expression of intermediate proteins. Several UTR sequences are patented and used frequently in laboratories. We present a novel model UTRGAN, a Generative Adversarial Network (GAN)-based model designed to generate 5′ UTR sequences coupled with an optimization procedure to ensure a target property such as high expression for a target gene sequence or high ribosome load. We rigorously analyze and show that the model can generate sequences that mimic various properties of natural UTR sequences. Then, we show that the optimization procedure yields sequences that are expected to yield 32% higher expression (up to 7-fold) on a set of target genes and 12% higher ribosome load on average on a set of generated 5′ UTRs (up to 90% for the best 5′ UTR), compared to the initially generated UTR sequences. We also demonstrate that when there is a single target gene of interest, the expected expression increases by 55% on average and up to 100% for certain genes (up to 15-fold for the best 5′ UTR).

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Section: Resultsmentioning

confidence: 99%

UTRGAN: Learning to Generate 5’ UTR Sequences for Optimized Translation Efficiency and Gene Expression

Barazandeh

Furkan

Hincer

et al. 2023

Preprint

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“…In our identified pathways, the “Immune System” is prominent in the development of hypertension [ 65 ]. The “interferon gamma signaling” pathway modulates immune responses as well as influences hypertension [ 66 ]. The “T cell receptor signaling” and “Apoptosis” pathways are involved in diabetes progression [ 67 , 68 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Comorbidities, Genomic Associations, and Molecular Mechanisms for COVID‐19 Using Bioinformatics Approaches

Omit

Akhter

Rana

et al. 2023

BioMed Research International

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Several studies have been done to identify comorbidities of COVID-19. In this work, we developed an analytical bioinformatics framework to reveal COVID-19 comorbidities, their genomic associations, and molecular mechanisms accomplishing transcriptomic analyses of the RNA-seq datasets provided by the Gene Expression Omnibus (GEO) database, where normal and infected tissues were evaluated. Using the framework, we identified 27 COVID-19 correlated diseases out of 7,092 collected diseases. Analyzing clinical and epidemiological research, we noticed that our identified 27 diseases are associated with COVID-19, where hypertension, diabetes, obesity, and lung cancer are observed several times in COVID-19 patients. Therefore, we selected the above four diseases and performed assorted analyses to demonstrate the association between COVID-19 and hypertension, diabetes, obesity, and lung cancer as comorbidities. We investigated genomic associations with the cross-comparative analysis and Jaccard’s similarity index, identifying shared differentially expressed genes (DEGs) and linking DEGs of COVID-19 and the comorbidities, in which we identified hypertension as the most associated illness. We also revealed molecular mechanisms by identifying statistically significant ten pathways and ten ontologies. Moreover, to understand cellular physiology, we did protein-protein interaction (PPI) analyses among the comorbidities and COVID-19. We also used the degree centrality method and identified ten biomarker hub proteins (IL1B, CXCL8, FN1, MMP9, CXCL10, IL1A, IRF7, VWF, CXCL9, and ISG15) that associate COVID-19 with the comorbidities. Finally, we validated our findings by searching the published literature. Thus, our analytical approach elicited interconnections between COVID-19 and the aforementioned comorbidities in terms of remarkable DEGs, pathways, ontologies, PPI, and biomarker hub proteins.

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“…Additionally, splenic CD8Ts from hypertensive mice can generate salt sensitive hypertension in recipients (97). We further found the cytokine IFNγ was critical for this infiltration to take place in the DOCA + Salt model (10) and adoptive transfer models of hypertension (22). Of note, IFNγ from CD8 + Ts stimulates the IFNγ receptor expressed within the distal convoluted tubule to promote interaction between the CD8 + T and tubule (10).…”

Section: Adaptive Immunity and The Kidney In Hypertensionmentioning

confidence: 98%

“…We further demonstrated that IFNγ is critical for mediating CD8 + T cell infiltration and interaction within the kidney, driving increased sodium retention ( 10 ). Adoptive transfer of primary CD8 + T cells from hypertensive mice is able to induce salt sensitivity hypertension(SSH) in WT mice, however, adoptive transfer of primary CD8 + T cells from IFNγ KO hypertensive mice failed to induce SSHTN in WT mice ( 22 ). Collectively these data evidence the critical role of IFNγ in mediating immune-driven hypertension.…”

Section: Immunity Inflammation and Hypertensionmentioning

confidence: 99%

The link between immunity and hypertension in the kidney and heart

Benson

Guo²,

Deck³

et al. 2023

Front. Cardiovasc. Med.

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Hypertension is the primary cause of cardiovascular disease, which is a leading killer worldwide. Despite the prevalence of this non-communicable disease, still between 90% and 95% of cases are of unknown or multivariate cause (“essential hypertension”). Current therapeutic options focus primarily on lowering blood pressure through decreasing peripheral resistance or reducing fluid volume, but fewer than half of hypertensive patients can reach blood pressure control. Hence, identifying unknown mechanisms causing essential hypertension and designing new treatment accordingly are critically needed for improving public health. In recent years, the immune system has been increasingly implicated in contributing to a plethora of cardiovascular diseases. Many studies have demonstrated the critical role of the immune system in the pathogenesis of hypertension, particularly through pro-inflammatory mechanisms within the kidney and heart, which, eventually, drive a myriad of renal and cardiovascular diseases. However, the precise mechanisms and potential therapeutic targets remain largely unknown. Therefore, identifying which immune players are contributing to local inflammation and characterizing pro-inflammatory molecules and mechanisms involved will provide promising new therapeutic targets that could lower blood pressure and prevent progression from hypertension into renal or cardiac dysfunction.

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IFN-γ Contributes to the Immune Mechanisms of Hypertension

Cited by 15 publications

References 121 publications

UTRGAN: Learning to Generate 5’ UTR Sequences for Optimized Translation Efficiency and Gene Expression

UTRGAN: Learning to Generate 5’ UTR Sequences for Optimized Translation Efficiency and Gene Expression

Identification of Comorbidities, Genomic Associations, and Molecular Mechanisms for COVID‐19 Using Bioinformatics Approaches

The link between immunity and hypertension in the kidney and heart

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