Computational identification of potential transcriptional regulators of TGF-ß1 in human atherosclerotic arteries

Abstract

TGF-ß is protective in atherosclerosis but deleterious in metastatic cancers. Our aim was to determine whether TGF-ß transcriptional regulation is tissue-specific in early atherosclerosis. The computational methods included 5 steps: (i) from microarray data of human atherosclerotic carotid tissue, to identify the 10 best co-expressed genes with TGFB1 (TGFB1 gene cluster), (ii) to choose the 11 proximal promoters, (iii) to predict the TFBS shared by the promoters, (iv) to identify the common TFs co-expressed with the TGFB1 gene cluster, and (v) to compare the common TFs in the early lesions to those identified in advanced atherosclerotic lesions and in various cancers. Our results show that EGR1, SP1 and KLF6 could be responsible for TGFB1 basal expression, KLF6 appearing specific to atherosclerotic lesions. Among the TFs co-expressed with the gene cluster, transcriptional activators (SLC2A4RG, MAZ) and repressors (ZBTB7A, PATZ1, ZNF263) could be involved in the fine-tuning of TGFB1 expression in atherosclerosis.

RETRACTED: Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes

“…No data is available about the influence of KLF6 on macrophages in atherosclerosis. However, a recent computer simulation showed that KLF6 could be responsible for TGF-β1 basal expression in vessels and KLF6 activation is associated with the development of atherosclerotic plaques, the evidence favoring the potential atherogenic role of this transcription factor [123].…”

PATZ1 acts as a tumor suppressor in thyroid cancer via targeting p53-dependent genes involved in EMT and cell migration

“…Consistent with the involvement of PATZ1 in EMT, it has been recently shown that PATZ1 is part of a group of transcription factors, including proteins already linked to EMT, such as EGR-1, Sp1, Sp2, NME1, CTCF, PLAG1 and WT1, potential regulators of TGF-β1 [34]. PATZ1 reintroduction in BC-PAP and FRO cells also affected cell proliferation, suggesting a possible role for PATZ1 in this cellular function depending on the cellular context.…”

The Relationship of Plasma miR-29a and Oxidized Low Density Lipoprotein with Atherosclerosis

“…Further study showed that miR-29a adjusted collagen synthesis dependent on transforming growth factor-betas (TGF-ß) signaling pathway [28]. Multiple researches demonstrated TGF-ß played an important role in atherosclerosis [29,30]. Previous studies have shown that miR-29 up-regulation was associated with vascular abnormality [31] and miR-29 was involved in vascular smooth muscle cell migration and proliferation by mediating an epigenetic mechanism, which is related to atherosclerosis [32].Our results were also showed miR-29 levels were higher in atherosclerosis patient than normal controls, which was similar to previous research results.…”