title: Lipocalin-7 is a matricellular regulator of angiogenesis.
abstract: BACKGROUND
  Matricellular proteins are extracellular regulators of cellular adhesion, signaling and performing a variety of physiological behaviors such as proliferation, migration and differentiation. Within vascular microenvironments, matricellular proteins exert both positive and negative regulatory cues to vascular endothelium. The relative balance of these matricellular cues is believed to be critical for vascular homeostasis, angiogenesis activation or angiogenesis resolution. However, our knowledge of matricellular proteins within vascular microenvironments and the mechanisms by which these proteins impact vascular function remain largely undefined. The matricellular protein lipocalin-7 (LCN7) is found throughout vascular microenvironments, and circumstantial evidence suggests that LCN7 may be an important regulator of angiogenesis. Therefore, we hypothesized that LCN7 may be an important regulator of vascular function.
  
  
  RESULTS
  To test this hypothesis, we examined the effect of LCN7 overexpression, recombinant protein and gene knockdown in a series of in vitro and in vivo models of angiogenesis. We found that overexpression of LCN7 in MB114 and SVEC murine endothelial cell lines or administration of highly purified recombinant LCN7 protein increased endothelial cell invasion. Similarly, LCN7 increased angiogenic sprouting from quiescent endothelial cell monolayers and ex vivo aortic rings. Moreover, LCN7 increased endothelial cell sensitivity to TGF-β but did not affect sensitivity to other pro-angiogenic growth factors including bFGF and VEGF. Finally, morpholino based knockdown of LCN7 in zebrafish embryos specifically inhibited angiogenic sprouting but did not affect vasculogenesis within injected embryos.
  
  
  CONCLUSIONS
  No functional analysis has previously been performed to elucidate the function of LCN7 in vascular or other cellular processes. Collectively, our results show for the first time that LCN7 is an important pro-angiogenic matricellular protein of vascular microenvironments.
authors.affiliation: Department of Biology, Indiana State University, Terre Haute, Indiana, United States of America.
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Brown
authors.forename: Mariam
authors.initials: M
authors.lastname: Alawoki
authors.forename: Mary E
authors.initials: ME
authors.lastname: Crawford
authors.forename: Tiffany
authors.initials: T
authors.lastname: Reida
authors.forename: Allison
authors.initials: A
authors.lastname: Sears
authors.forename: Tory
authors.initials: T
authors.lastname: Torma
authors.forename: Allan R
authors.initials: AR
authors.lastname: Albig
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D066298:In Vitro Techniques; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D054834:Lipocalins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; C484283:Tinagl1 protein, mouse; D016212:Transforming Growth Factor beta