Mechanosensory Pathways in Angiocrine Mediated Tissue Regeneration - Mechanical and Chemical Signaling in Angiogenesis - page 37

Fig. 10 Id1 upregulation in LSECs is essential for liver regeneration. a Compared with their
wild-type (WT) littermates, Id1 -/- mice manifest impaired regeneration in liver mass, which fails
to be rescued by VEGF-A 164 administration (n = 5). b The liver SEC-dependent stimulation of
hepatocyte proliferation was specifically inhibited by Id1 gene knockdown. Scr, scrambled liver
SEC-conditioned medium (n = 4). c Transplantation of Id1 +/+ LSECs restores the regeneration of
mass in the Id -/- liver (n = 4). Dashed line, level of Id1 -/- liver without endothelial cell

transplantation. *P,0.05, versus Id1 -/- a; **P,0.01, versus Id1 -/- with VEGF 164 a. Scale bars,

50 mm b and 20 mm. Error bars, SEM

To identify endothelial-derived angiocrine factors that induce liver regenera-
tion, we analyzed LSECs purified from the wild-type and Id1 +/+ mice 48 h after
partial hepatectomy. The expression of Wnt2 and HGF, but not other hepatic
trophogens expressed by LSECs, such as Wnt9B and thrombomodulin, was
drastically diminished in Id +/+ LSECs (Fig. 11 a). These results suggest that Id1
upregulation in LSECs initiates hepatocyte proliferation through inducing Wnt2
and HGF expression. To test this hypothesis, on day 2 after partial hepatectomy,
we engrafted Id1 -/- LSECs transduced with Wnt2, HGF or both into the Id1 -/-