A tale of two transcription factors: NF-kB and HIF crosstalk

Abstract

Introduction Hypoxia-inducible factor is a key transcriptional factor involved in the cellular response to low levels of oxygen, hypoxia. Moreover, hypoxiainducible factor has been recently associated with a role in inflammation and immunity. Importantly, hypoxiainducible factor is regulated by the major inflammatory responsive transcription factor, nuclear factor-κB. These two major pathways have been intimately linked. On one hand, they share a number of common target genes; on the other hand, physical interactions between hypoxiainducible factor subunits and nuclear factor-κB have been observed. Even though the role of nuclear factor-κB over hypoxia-inducible factor is fairly well-known, the involvement of hypoxia-inducible factor over the nuclear factor-κB pathway is not. Given the overlap between these pathways, it would not be surprising to find a functional involvement of hypoxiainducible factor in processes where nuclear factor-κB is involved. In this review, we will describe the communalities between hypoxia-inducible factor and nuclear factor-κB pathways, highlighting the crosstalk that occurs in a variety of conditions. Conclusion Taken together all the communalities between hypoxia-inducible factor and nuclear factor-κB pathways, there is no doubt that a cross-

Hemorrhage Exacerbates Radiation Effects on Survival, Leukocytopenia, Thrombopenia, Erythropenia, Bone Marrow Cell Depletion and Hematopoiesis, and Inflammation-Associated microRNAs Expression in Kidney

“…One of the Ras genes, Kras was reported as a well-established target of let-7 and also demonstrated to be a part of the MAPK signaling pathway [ 51 ] Upregulated let-7 in response to CI may damage the kidney blood cells that involved in proliferation and differentiation when exposed to radiation [ 48 ]. Acute kidney injury induces NF-κB, one of the major inflammation mediators and also the transcriptional factor HIF-1 that involved in the cellular response to low level of oxygen, hypoxia [ 52 , 53 ]. Recently, the HIF-1 has been shown to play a role in inflammation, indicating that both HIF-1 and NF-κB pathways were intimately linked.…”

“…These two major pathways share common target genes including EPO that is produced by the kidney which regulates red blood cell production in the bone marrow as indicated in our bioinformatics analysis. Studies have also reported physical interaction between these molecules [ 53 , 54 ]. NF-kB has been shown to directly activate let-7e during osteoclast differentiation [ 55 ].…”

NF‐κB and HIF crosstalk in immune responses

“…As part of this complex interaction, an extensive crosstalk between the two main molecular players involved, HIF (hypoxia) and NF‐κB (inflammation), has been reported. This crosstalk includes common activating stimuli, and shared regulators and targets, as recently reviewed . The hypoxia‐induced activation of the NF‐κB pathway was first reported in 1994 , and thereafter a number of studies followed to elucidate the mechanisms underlying this activation.…”

Hypoxia Induced NF-κB

“…In this review we will focus on the pathways described for the activation of NF-κB in hypoxia and describe the roles of NF-κB in the cellular response to low oxygen. Of note, an extensive crosstalk exists between HIF and NF-κB, which has been recently reviewed elsewhere [ 7 , 8 , 9 ].…”