Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.

PLoS Neglected Tropical Diseases
Aniekanabassi N UdokoPius N Nde

Abstract

The molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quanti...Continue Reading

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Citations

Jul 28, 2020·Virulence·Lissa Cruz-SaavedraJuan David Ramírez
Jul 26, 2018·Biomedicines·Leandra B JonesQiana L Matthews
Oct 2, 2019·International Journal of Molecular Sciences·Tatiana Araújo SilvaClaudia Magalhães Calvet
Mar 7, 2021·International Journal of Molecular Sciences·Kayla J RayfordPius N Nde
Oct 18, 2016·JACC. Basic to Translational Science·Jian-Jun WenNisha Jain Garg
Sep 11, 2021·Frontiers in Cellular and Infection Microbiology·Kristyn A HoffmanKathryn M Jones

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Datasets Mentioned

BETA
GSE75821

Methods Mentioned

BETA
PCR
transgenic
Fluorescence
Fluorescence Microscopy
Enzyme Linked Immunosorbent Assay
ELISArray
ELISA
chips
confocal microscopy
nuclear translocation

Software Mentioned

CFX manager
CAStream
PHCM
GENEMANIA
CYTOSCAPE
WEBGESTALT
Partek Genomics Suite

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