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P‐II‐02
Leukemia Inhibitory Factor Gene and Vascular Endothelial Growth Factor Protein can Module Embryonic Fibroblastic Differentiation via GP130‐STAT and MAPK Signal Transduction Pathways
Author(s) -
Akita S,
Akino K,
Fukui M
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.abstractr.x
Subject(s) - leukemia inhibitory factor , transfection , vascular endothelial growth factor , microbiology and biotechnology , basic fibroblast growth factor , mapk/erk pathway , embryonic stem cell , vascular endothelial growth factor a , growth factor , biology , chemistry , phosphorylation , cell culture , cancer research , biochemistry , vegf receptors , gene , genetics , receptor
The combined application of cytokines on embryonic fibroblasts and dermal substitute were extensively studied for optimal skin defect coverage. Signalling of combined treatment of leukemia inhibitory factor (LIF) and vascular endothelial factor (VEGF) were elucidated and subsequently the in vivo applications of both were tested in an artificial dermal substitute. Mouse embryonic fibroblast cells, BALB‐3T3, were stably transfected with mouse full length LIF cDNA and added to various doses of VEGF for detection of signalling interaction. LIF‐transfected cells and VEGF treatment were tested with pig‐tendon derived collagen dermal substitute in the backs of BALB/c male mice for 14 days. LIF‐transfected cells as well as vector‐transfected fibroblasts significantly proliferated by 1, 10, or 100 nM VEGF on days 3 and 5. LIF‐transfected cells showed rapid phosphorylation of STAT 3 from 1 minute to 60 minutes after VEGF treatment, while vector‐transfected cells failed to induce such phosphorylation after VEGF treatment. Erk MAP kinase phosphorylation was observed from 1 to 15 minutes in LIF‐transfected and 10 nM of VEFG and 1 to 30 minutes in LIF‐transfected and 100 nM VEFG treatments. In in vivo analyses, LIF‐transfected embryonic fibroblasts with 50 μg of VEGF markedly enhanced collagen I expression and CD 34 angiogenic marker on days 7 and 14. LIF transfection induced constitutive STAT signaling and enhanced phosphorylated‐Erk MAP kinase with exogenous VEGF. In vivo study revealed that the combined application of LIF‐transfection of embryonic fibroblasts with an angiogenic factor such as VEGF in the template of an artificial dermis.