Transcriptomic analysis identifies novel targets for individual bone morphogenetic protein type 1 receptors in endothelial cells

FASEB J. 2021 Mar;35(3):e21386. doi: 10.1096/fj.202002071R.

Abstract

Bone Morphogenetic Protein (BMP) signaling regulates diverse biological processes. Upon ligand binding, BMP receptors (BMPRs) phosphorylate SMAD1/5 and other noncanonical downstream effectors to induce transcription of downstream targets. However, the precise role of individual BMP receptors in this process remains largely unknown due to the complexity of downstream signaling and the innate promiscuity of ligand-receptor interaction. To delineate unique downstream effectors of individual BMPR1s, we analyzed the transcriptome of human umbilical endothelial cells (HUVECs) expressing three distinct constitutively active BMPR1s of which expression was detected in endothelial cells (ECs). From our analyses, we identified a number of novel downstream targets of BMPR1s in ECs. More importantly, we found that each BMPR1 possesses a distinctive set of downstream effectors, suggesting that each BMPR1 is likely to retain unique function in ECs. Taken together, our analyses suggest that each BMPR1 regulates downstream targets non-redundantly in ECs to create context-dependent outcomes of the BMP signaling.

Keywords: ALK2; BMP signaling; BMPR1; endothelial cell; transcriptomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I / genetics
  • Animals
  • Bone Morphogenetic Protein Receptors, Type I / physiology*
  • Cells, Cultured
  • Gene Expression Profiling / methods*
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Smad1 Protein / physiology
  • Smad5 Protein / physiology

Substances

  • Smad1 Protein
  • Smad5 Protein
  • ACVR1 protein, human
  • Activin Receptors, Type I
  • Bone Morphogenetic Protein Receptors, Type I