| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T27186 | ||||
| Target Name | Placenta growth factor | ||||
| Target Type | Clinical Trial |
||||
| Action against Disease Model | R7334 | Genentech R7334 anti-PlGF h uMAb solid t uMors | Drug Info | ||
| The Effect of Target Knockout, Knockdown or Genetic Variations | We investigated the function of placental growth factor (PlGF) in experimental models of acute colitis. Acute colonic damage was induced in PlGF knock-out ((-/-)) mice and PlGF wild-type ((+/+)) mice by dextran sodi uM sulfate (DSS) and trinitrobenzenesulfonic acid (TNBS). The concentrations of PlGF and VEGF were measured in distal colonic lysates using an enzyme-linked immunosorbent assay. Colonic injury was evaluated by assessing colon length, colonocyte apoptosis (by terminal dUTP nick-end labeling), colonic cytokine production and histological score. Infiltration of polymorphonuclear cells was determined by assaying myeloperoxidase (MPO) activity. In a separate experiment, recombinant PlGF was administered to PlGF(-/-) mice by adenoviral transfer before DSS administration. Mucosal vascularization was quantified by computerized morphometric analysis of CD31-stained distal colonic sections. Colonic mucosal hypoxia was visualized by pimonidazole staining. Both VEGF and PlGF were upregulated during acute colitis. In addition, compared with PlGF(+/+) controls, PlGF(-/-) mice showed a significant increase in weight loss and colonic shortening during both DSS and TNBS colitis. This correlated with enhanced colonocyte apoptosis, elevated colonic cytokine levels and increased histological damage score, but not with enhanced inflammatory cell infiltration (MPO activity). The increased morbidity of PlGF(-/-) mice during DSS colitis was preventable by adenovirus (Ad)-mediated overexpression of PlGF. After the administration of DSS, strongly reduced mucosal angiogenesis was observed in PlGF(-/-) mice compared with PlGF(+/+) mice. This was associated with an early increase in intestinal epithelial pimonidazole acc uMulation in PlGF(-/-) mice, suggesting a function of enhanced epithelial hypoxia in the observed differences between the two groups. In s uMmary, our data show that the absence of PlGF strongly inhibits mucosal intestinal angiogenesis in acute colitis, which is associated with an early increase in intestinal epithelial hypoxia and aggravation of the course of the disease | ||||
| References | |||||
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.