HRF, a putative basic helix-loop-helix-PAS-domain transcription factor is closely related to hypoxia-inducible factor-1α and developmentally expressed in blood vessels
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Abstract
Transcription factors of the bHLH-PAS protein family are important regulators of developmental
processes such as neurogenesis and tracheal development in invertebrates. Recently
a bHLH-PAS protein, named trachealess (trl) was identified as a master regulator of
tracheogenesis. Hypoxia-inducible factor, HIF-1 alpha, is a vertebrate relative of
trl which is likely to be involved in growth of blood vessels by the induction of
vascular endothelial growth factor (VEGF) in response to hypoxia. In the present study
we describe mRNA cloning and mRNA expression pattern of mouse HIF-related factor (HRF),
a novel close relative of HIF-1 alpha which is expressed most prominently in brain
capillary endothelial cells and other blood vessels as well as in bronchial epithelium
in the embryo and the adult. In addition, smooth muscle cells of the uterus, neurons,
brown adipose tissue and various epithelial tissues express HRF mRNA as well. High
expression levels of HRF mRNA in embryonic choroid plexus and kidney glomeruli, places
where VEGF is highly expressed, suggest a role of this factor in VEGF gene activation
similar to that of HIF-1 alpha. Given the similarity between morphogenesis of the
tracheal system and the vertebrate vascular system, the expression pattern of HRF
in the vasculature and the bronchial tree raises the possibility that this family
of transcription factors may be involved in tubulogenesis.