Molecular insights on the proangiogenic effects of VEGF like growth factor derived from horseshoe crab perivitelline...

The current study investigated the proangiogenic effects of fraction VII of perivitelline fluid (hscPVF-VEGF) obtained from the late-stage embryos of Indian horseshoe crab (Tachypleus gigas; Müller) using human umbilical cord tissue-derived MSCs (hUCMSCs). Angiogenic potential of hscPVF-VEGF was investigated by analyzing transcripts of signature angiogenic markers, key transcription factors and matrix metalloproteases. Molecular docking studies were performed to predict the binding site of hscPVF-VEGF with the VEGF receptor (VEGFR). hscPVF-VEGF significantly upregulated VEGF, vWF, and downregulated sFlt-1. Significant increase in transcriptional levels of HOXA7, HOXB3, HOXB5, CD31, MMP2, and MMP9 further elucidated the molecular mechanism underlying the angiogenic ability of hscPVF-VEGF. Wound healing assay revealed the migratory potential of hscPVF-VEGF. Molecular docking studies predicted that hscPVF-VEGF may modulate hVEGFR activity by binding in a pocket within the extracellular domains (D5, D6, and D7) distal to the VEGF binding site (D2 and D3). This study infers the potential and molecular mechanism of hscPVF-VEGF inducing angiogenic differentiation in hUCMSCs, suggesting clinical application of a recombinant form of hsPVF-VEGF in disorders with dysfunctional angiogenesis.