title: Sonic hedgehog secreted by neurons regulates angiopoietin expression in neighboring fibroblasts.
abstract: Lately, the importance of the communication between different cell types and the understanding of the cell communication pathway has been emphasized, as it may provide a novel therapeutic strategy for the regeneration of damaged tissue. In the present study, we suggest that sonic hedgehog (Shh) is a mediator of cell communication between neurons and fibroblasts. Recombinant Shh (rShh) affected the expression of the angiogenic factors, angiopoietin (Ang)-1 and Ang-2, in fibroblasts, but not in neurons or neural progenitor cells (NPCs). The expression of the Shh downstream transcription factor, Gli1, was markedly increased in neurons and NPCs, indicating that neurons and NPCs responded to rShh. However, rShh did not affect Ang-1 and Ang-2 expression in neurons and NPCs. It should be noted that Shh was strongly expressed in neurons, but that Shh expression was undetectable in fibroblasts. We performed a co-culture assay using neurons and fibroblasts to investigate whether the expression of Ang-1 and Ang-2 is regulated by cell communication, without rShh treatment. Ang-1 expression in fibroblasts was markedly upregulated by co-culture with neurons, whereas Ang-2 expression was decreased by co-culture with neurons. Moreover, when an Shh-neutralizing antibody was added, this effect was diminished. Collectively, our data suggest that Shh-expressing neurons regulate angiopoietin expression in neighboring fibroblasts in a paracrine manner.
authors.affiliation: National Research Laboratory of Regenerative Sexual Medicine, Department of Urology, Inha University School of Medicine, Incheon, Republic of Korea.
authors.forename: Woo Jean
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine and Innovative Research Institute for Cell Therapy, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Sae-Won
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Division of Pharmaceutical Biosciences, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kyu-Won
authors.initials: KW
authors.lastname: Kim
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002450:Cell Communication; D018920:Coculture Techniques; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D041681:NIH 3T3 Cells; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467628:Angpt1 protein, mouse; D000906:Antibodies; D053823:Hedgehog Proteins; D011994:Recombinant Proteins; C465570:Shh protein, mouse