Home Blog of Signal Transduction Protein Tyrosine Kinase TAM receptors (Tyro-3,Axl,and Mertk) Growth Arrest Specific Protein (Gas)-6/AXL Signaling Induces Preeclampsia (PE) in Rats

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Growth Arrest Specific Protein (Gas)-6/AXL Signaling Induces Preeclampsia (PE) in Rats

Preeclampsia (PE) is a complicated obstetric complication characterized by increased blood pressure, decreased trophoblast invasion, and inflammation. The growth arrest-specific 6 (Gas6) protein is known to induce dynamic cellular responses and is elevated in PE. Gas6 binds to the AXL tyrosine kinase receptor and AXL-mediated signaling is implicated in proliferation and migration observed in several tissues. Our laboratory utilized Gas6 to induce preeclamptic-like conditions in pregnant rats. Our objective was to determine the role of Gas6/AXL signaling as a possible model of PE. Briefly, pregnant rats were divided into 3 groups that received daily intraperitoneal injections (from gestational day 7.5-17.5) of PBS, Gas6, or Gas6 + R428 (an AXL inhibitor administered from gestational day 13.5-17.5). Animals dispensed Gas6 experienced elevated blood pressure, increased proteinuria, augmented caspase-3 mediated placental apoptosis and diminished trophoblast invasion. Gas6 also enhanced expression of several PE related genes and a number of inflammatory mediators. Gas6 further enhanced placental oxidative stress and impaired mitochondrial respiration. Each of these PE related characteristics were ameliorated in dams and/or their placentae when AXL inhibition by R428 occurred in tandem with Gas6 treatment. We conclude that Gas6 signaling is capable of inducing PE and that inhibition of AXL prevents disease progression in pregnant rats. These results provide insight into pathways associated with PE that could be useful in the clarification of potential therapeutic approaches.

Related Products

Cat.No. Product Name Information
S2841 Bemcentinib (R428) Bemcentinib (R428, BGB324) is an inhibitor of Axl with IC50 of 14 nM, >100-fold selective for Axl versus Abl. Selectivty for Axl is also greater than Mer and Tyro3 (50-to-100- fold more selective) and InsR, EGFR, HER2, and PDGFRβ (100- fold more selective).

Related Targets

TAM receptors (Tyro-3,Axl,and Mertk)