Inhibiting VEGFR-2 and Neutralizing VEGF-A in C. difficile Infection

To inhibit VEGFR-2, mice were treated with daily intraperitoneal injections of 100μl SU1498 (30 mg/kg in dimethyl sulfoxide, Sigma Aldrich, Inc.) or dimethyl sulfoxide alone starting on the day of C. difficile gavage and continuing daily for 3 days^{49 (link)}. To neutralize VEGF-A, mice were treated with intraperitoneal injection of 250 μg rat anti-mouse VEGF-A antibody (2G11–2A05) or the isotype control IgG2a (each at 12.5 mg/kg, Biolegend, Inc.)^{50 (link)} at 12 and 36 hours after C. difficile challenge. To stabilize HIF-1α prolyl hydroxylase, mice were treated with intraperitoneal injections of 100μl DMOG (400mg/kg in saline, Cayman Chemical) starting on the day of C. difficile gavage for 2 days.

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Huang J., Kelly C.P., Bakirtzi K., Gálvez J.A., Lyras D., Mileto S.J., Larcombe S., Xu H., Yang X., Shields K.S., Zhu W., Zhang Y., Goldsmith J.D., Patel I.J., Hansen J., Huang M., Yla-Herttuala S., Moss A.C., Paredes-Sabja D., Pothoulakis C., Shah Y.M., Wang J, & Chen X. (2018). Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis. Nature microbiology, 4(2), 269-279.

Publication 2018

SU1498 IgG2a

Anti antibody Cayman Dimethyl sulfoxide Gavage Igg2a Inhibit Intraperitoneal injections Isotype Mice Prolyl hydroxylase Saline Su1498 Vegf Vegfr 2

Corresponding Organization :

Other organizations : Beth Israel Deaconess Medical Center, Harvard University, University of California, Los Angeles, Monash University, Australian Regenerative Medicine Institute, Massachusetts General Hospital, Boston Children's Hospital, Icahn School of Medicine at Mount Sinai, Sixth Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, University of Eastern Finland, Kuopio University Hospital, Universidad Andrés Bello, University of Michigan–Ann Arbor

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Variable analysis

independent variables

Treatment with SU1498 (30 mg/kg in dimethyl sulfoxide)
Treatment with rat anti-mouse VEGF-A antibody (2G11–2A05) (12.5 mg/kg)
Treatment with DMOG (400mg/kg in saline)

dependent variables

Inhibition of VEGFR-2
Neutralization of VEGF-A
Stabilization of HIF-1α prolyl hydroxylase

control variables

Dimethyl sulfoxide alone
Isotype control IgG2a (12.5 mg/kg)

positive controls

Dimethyl sulfoxide alone
Isotype control IgG2a (12.5 mg/kg)

negative controls

None specified

Annotations

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