Positive feedback control for reinforcing VEGF signaling
VEGF signaling is a key pathway for angiogenesis. Whereas the negative feedback control to suppress excessive VEGF signaling is well known, the positive feedback control for augmenting VEGF signaling remains poorly elucidated. A KAIST research team has recently found positive feedback regulators of VEGF signaling consisting of SoxF members, Sox7 and Sox17.
The Sox family is fundamental for organogenesis and many Sox members frequently cooperate. Sox members cooperate variously depending on the context: redundantly, sequentially, or complementarily. The KAIST team led by Injune Kim unveils a novel cooperation of Sox members for angiogenesis, new blood vessel formation.
This vascular biology team found that loss of any two copies of Sox7 and Sox17 genes in mouse embryo resulted in angiogenic defects, suggesting that Sox7 and Sox17 belonging to the SoxF subgroup genetically cooperates for developmental angiogenesis. VEGF, one of the most powerful stimulators of angiogenesis, upregulated both Sox7 and Sox17 in angiogenic endothelial cells. Both Sox7 and Sox17 increased VEGFR2, the VEGF receptor expressed in endothelial cells. Thus, these results demonstrate that Sox7 and Sox17 jointly promote developmental angiogenesis with overlapping expression and function.
Interestingly, VEGF regulation of SoxF expression and SoxF regulation of VEGFR2 expression form a positive feedback loop as shown in the Figure below. This positive feedback control may be critical for generating sufficient angiogenic output from a weak VEGF cue. SoxF are key players in developmental angiogenesis by acting as positive feedback regulators of VEGF signaling.
for more information please refer to the published article:
Kim K, et al. Circulation Research 2016 119: 839-852
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