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Kidney Week

Abstract: PO0248

The Effect of ANG-3777 on In Vitro Cell Proliferation

Session Information

  • AKI Mechanisms - 3
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Paka, Latha, Angion Biomedica Corp, Uniondale, New York, United States
  • Goldberg, Itzhak D., Angion Biomedica Corp, Uniondale, New York, United States
Background

Hepatocyte growth factor (HGF) regulates tissue growth and development by inducing cell motility, proliferation and morphogenesis in multiple cell types including endothelial and epithelial cells. However, it has no effect on proliferation in fibroblasts. ANG-3777 is a novel molecule that exerts similar cytoprotective and regenerative effects as HGF. This study compared the effect of ANG-3777 with that of HGF in stimulating cell proliferation.

Methods

In vitro cell proliferation assays were conducted in triplicate using human umbilical vein endothelial cells (HUVEC), rat neuronal Schwann cells, and mouse fibroblasts. HUVEC and fibroblasts were exposed to 5 µM ANG-3777 or 25 ng/mL HGF for up to 24 hours. Schwann cells were exposed to increasing doses of ANG-3777 (up to 10 µM) or HGF (up to 100 ng/mL) for 16 to 24 hours to evaluate the effective concentration at 50% proliferative activity (EC50). Radiolabeled [3H]-thymidine incorporation was used as a measure of cell proliferation. An unpaired T-test was used to compare ANG-3777 or HGF versus vehicle (dimethyl sulfoxide) treatment.

Results

A statistically significant increase in cell proliferation (~3-fold) was observed in HUVECs exposed to ANG-3777 and HGF compared with vehicle (p<0.01; Figure 1). Similarly, Schwann cell proliferation increased in a concentration-dependent manner following exposure to ANG-3777 (EC50 0.012 µM) and HGF (EC50 6.5 ng/mL). In mouse fibroblasts (negative control), neither ANG-3777 nor HGF exposure stimulated cell proliferation compared with vehicle.

Conclusion

In vitro cell-based proliferation assays confirmed that the activity of ANG-3777 is comparable to that of HGF in inducing cell proliferation in HUVECs and rat Schwann cells with neither agent stimulating proliferation in mouse fibroblasts.