The GTPase-activating protein Rap1GAP: A new player to modulate Ret signaling

Paratcha, Gustavo; Ledda, Fernanda

doi:10.1038/cr.2010.143

Cited by 7 publications

(2 citation statements)

References 14 publications

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“…The top up-regulated genes after exposure to COVID-19 during pregnancy included ras-associated protein-1 GTPase-activating-protein (RAP1GAP), pro-platelet basic protein (PPBP), and histone cluster 1, H1b (HIST1H1B). RAP1GAP plays a key role in the control of adherens junctions at different levels that takes part in cell adhesion and cell-cell junction formation ( 24 ) and neuronal differentiation ( 25 ). In animal models, RAP1GAP mediates angiotensin II-induced cardiomyocyte hypertrophy by inhibiting autophagy and increasing oxidative stress ( 26 ).…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Infection During Pregnancy Induces Differential Gene Expression in Human Cord Blood Cells From Term Neonates

et al. 2022

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BackgroundThe COVID-19 pandemic continues worldwide with fluctuating case numbers in the United States. This pandemic has affected every segment of the population with more recent hospitalizations in the pediatric population. Vertical transmission of COVID-19 is uncommon, but reports show that there are thrombotic, vascular, and inflammatory changes in the placenta to which neonates are prenatally exposed. Individuals exposed in utero to influenza during the 1918 pandemic had increased risk for heart disease, kidney disease, diabetes, stomach disease and hypertension. Early exposure of COVID-19 during fetal life may lead to altered gene expression with potential long-term consequences.ObjectiveTo determine if gene expression is altered in cord blood cells from term neonates who were exposed to COVID-19 during pregnancy and to identify potential gene pathways impacted by maternal COVID-19.MethodsCord blood was collected from 16 term neonates (8 exposed to COVID-19 during pregnancy and 8 controls without exposure to COVID-19). Genome-wide gene expression screening was performed using Human Clariom S gene chips on total RNA extracted from cord blood cells.ResultsWe identified 510 differentially expressed genes (374 genes up-regulated, 136 genes down-regulated, fold change ≥1.5, p-value ≤ 0.05) in cord blood cells associated with exposure to COVID-19 during pregnancy. Ingenuity Pathway Analysis identified important canonical pathways associated with diseases such as cardiovascular disease, hematological disease, embryonic cancer and cellular development. Tox functions related to cardiotoxicity, hepatotoxicity and nephrotoxicity were also altered after exposure to COVID-19 during pregnancy.ConclusionsExposure to COVID-19 during pregnancy induces differential gene expression in cord blood cells. The differentially expressed genes may potentially contribute to cardiac, hepatic, renal and immunological disorders in offspring exposed to COVID-19 during pregnancy. These findings lead to a further understanding of the effects of COVID-19 exposure at an early stage of life and its potential long-term consequences as well as therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

COVID-19 Infection During Pregnancy Induces Differential Gene Expression in Human Cord Blood Cells From Term Neonates

et al. 2022

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“…However, IFITM3 knockdown did not cause any skeletal phenotype; the gene expression was described to affect MAPK pathway activation and influence TGF-β-Smads-MAPK pathway [ 44 , 45 ]. Similarly, one of the strongest candidate DEGs was the RAP1GAP gene, which encodes an enzyme that binds to the Rep protein and triggers numerous signaling pathways, including the Ras-Raf-MAPK (ERK1/2) cascade [ 46 , 47 ]. Recently, a connection between OI and alterations in the ERK1/2 pathway was described.…”

Section: Discussionmentioning

confidence: 99%

RNA sequencing analysis reveals increased expression of interferon signaling genes and dysregulation of bone metabolism affecting pathways in the whole blood of patients with osteogenesis imperfecta

et al. 2020

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Background Osteogenesis imperfecta (OI) is a rare genetic disorder in which the patients suffer from numerous fractures, skeletal deformities and bluish sclera. The disorder ranges from a mild form to severe and lethal cases. The main objective of this pilot study was to compare the blood transcriptional landscape of OI patients with COL1A1 pathogenic variants and their healthy relatives, in order to find out different gene expression and dysregulated molecular pathways in OI. Methods We performed RNA sequencing analysis of whole blood in seven individuals affected with different OI severity and their five unaffected relatives from the three families. The data was analyzed using edgeR package of R Bioconductor. Functional profiling and pathway analysis of the identified differently expressed genes was performed with g:GOSt and MinePath web-based tools. Results We identified 114 differently expressed genes. The expression of 79 genes was up-regulated, while 35 genes were down-regulated. The functional analysis identified a presence of dysregulated interferon signaling pathways (IFI27, IFITM3, RSAD12, GBP7). Additionally, the expressions of the genes related to extracellular matrix organization, Wnt signaling, vitamin D metabolism and MAPK-ERK 1/2 pathways were also altered. Conclusions The current pilot study successfully captured the differential expression of inflammation and bone metabolism pathways in OI patients. This work can contribute to future research of transcriptional bloodomics in OI. Transcriptional bloodomics has a strong potential to become a major contributor to the understanding of OI pathological mechanisms, the discovery of phenotype modifying factors, and the identification of new therapeutic targets. However, further studies in bigger cohorts of OI patients are needed to confirm the findings of the current work.

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