Lymphatic-specific intracellular modulation of receptor tyrosine kinase signaling improves lymphatic growth and function.

ABSTRACT: Exogenous administration of lymphangiogenic growth factors is widely used to study changes in lymphatic function in pathophysiology. However, this approach can result in off-target effects, thereby generating conflicting data. To circumvent this issue, we modulated intracellular VEGF-C signaling by conditionally knocking out the lipid phosphatase PTEN using the Vegfr3 promoter to drive the expression of Cre-lox in lymphatic endothelial cells (LECs). PTEN is an intracellular brake that inhibits the downstream effects of the activation of VEGFR3 by VEGF-C. Activation of Cre-lox recombination in adult mice resulted in an expanded functional lymphatic network due to LEC proliferation that was independent of lymphangiogenic growth factor production. Furthermore, compared with lymp

SUBMITTER: Kataru RP 

PROVIDER: S-EPMC8567054 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature