A new role of transcription factor SOX17 as potential interaction partner of KLF4 and EGR-1 in human coronary artery smooth muscle cells and in differentiating mouse ES-cells

The development of the vascular network comprises tightly regulated
processes, involving vasculogenesis and angiogenesis. The cells,
which are mainly participating in these processes, are endothelial
cells and vascular smooth muscle cells, the latter ones especially
being important for the stability of blood vessels. Uncontrolled
proliferation of VSMCs contributes crucially to the development of
vascular disease, e.g. in the case of atherosclerosis. Two main
initiator factors of these processes are Low Densitiy Lipoprotein
(LDL) and Platelet Derived Growth Factor-BB (PDGF-BB). For this
reason, the VSMCs and the transcriptional regulation of their
proliferation, in response to LDL and PDGF-BB, build an important
target for therapeutical interventions. Sox17, a member of subgroup
F of the Sox family proteins, was for the first time detected in
vascular smooth muscle cells in different mouse tissues, like
liver, brain, heart, lung, spleen and kidney in vivo and in human
coronary artery smooth muscle cells in vitro. Moreover, a new
possible protein complex, consisting of SOX17, KLF4 and EGR-1, was
found in human coronary artery smooth muscle cells, as well as in 4
day old embryoid bodies. All members of this complex are induced by
PDGF-BB, a growth factor which becomes activated in angiogenesis
and pathological vascular conditions, stimulating the migration and
proliferation of vascular SMCs. By this the complex might be
involved in migration and proliferation of vascular SMCs, and
moreover in pathological vascular conditions, like the progression
of atherosclerosis. EGR-1 is known to be the key player in
mediating the transcriptional responses to PDGF-BB and LDL and has
already been implicated in progression of atherosclerosis. Because
of the fact, that a complex, consisting of Sox17, Klf4 and Egr-1,
was also observed to be formed in differentiating ES-cells (day 4),
supports a broader role of this protein complex in the
differentiation of cell-specific lineages during development, in
particular vascular smooth muscle cells and endoderm lineages. The
complex might have an inhibitory, as well as an activating role, as
Sox17, Klf4, and Egr-1 are known to behave bifunctional. Besides,
Sox17 seems to bind to -catenin during EB formation. At least this
could be an indication for an involvement of the complex in
modulating the wnt-signaling pathway during embryonic development.