The roles of ETS transcription factors in liver fibrosis

Zhang, Liye; Tan, Yong; Luo, Xinmei; Wu, Jiangfeng; Ni, Yi-Ran

doi:10.1007/s13577-022-00848-5

Cited by 1 publication

(1 citation statement)

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“…ETS transcription factors are associated with a number of cancers, including breast and leukaemia. ETS-1 is linked to liver fibrosis, where it is thought to be activated by Extracellular Signal-Regulated Kinases (ERK) signalling pathways, matrix remodelling, and cross talk with Transforming Growth Factor (TGF)-Suppressor of Mothers Against Decapentaplegic (SMAD) signalling [ 47 ]. Interestingly, there is evidence of significant cross-talk with regard to these transcription factors.…”

Section: Discussionmentioning

confidence: 99%

Orphan Nuclear Receptor Family 4A (NR4A) Members NR4A2 and NR4A3 Selectively Modulate Elements of the Monocyte Response to Buffered Hypercapnia

Phelan,

Reddan,

Shigemura

et al. 2024

IJMS

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Hypercapnia occurs when the partial pressure of carbon dioxide (CO2) in the blood exceeds 45 mmHg. Hypercapnia is associated with several lung pathologies and is transcriptionally linked to suppression of immune and inflammatory signalling through poorly understood mechanisms. Here we propose Orphan Nuclear Receptor Family 4A (NR4A) family members NR4A2 and NR4A3 as potential transcriptional regulators of the cellular response to hypercapnia in monocytes. Using a THP-1 monocyte model, we investigated the sensitivity of NR4A family members to CO2 and the impact of depleting NR4A2 and NR4A3 on the monocyte response to buffered hypercapnia (10% CO2) using RNA-sequencing. We observed that NR4A2 and NR4A3 are CO2-sensitive transcription factors and that depletion of NR4A2 and NR4A3 led to reduced CO2-sensitivity of mitochondrial and heat shock protein (Hsp)-related genes, respectively. Several CO2-sensitive genes were, however, refractory to depletion of NR4A2 and NR4A3, indicating that NR4As regulate certain elements of the cellular response to buffered hypercapnia but that other transcription factors also contribute. Bioinformatic analysis of conserved CO2-sensitive genes implicated several novel putative CO2-sensitive transcription factors, of which the ETS Proto-Oncogene 1 Transcription Factor (ETS-1) was validated to show increased nuclear expression in buffered hypercapnia. These data give significant insights into the understanding of immune responses in patients experiencing hypercapnia.

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Section: Discussionmentioning

confidence: 99%