The role of SDF1 in prostate epithelial morphogenesis

Autor(es)

Barbosa, Guilherme Oliveira ^[1] ; Augusto, Taize Machado ^[2] ; Bruni-Cardoso, Alexandre ^[3] ; Carvalho, Hernandes F. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Campinas, Dept Biol Estrut & Func, Inst Biol, Campinas, SP - Brazil

^[2] Fac Med Jundiai, Dept Clin, Rua Francisco Telles, Jundiai - Brazil

^[3] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sala Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 234, n. 5, p. 6886-6897, MAY 2019.
• Citações Web of Science: 0

Resumo

Androgens induce rat prostate induction from the urogenital sinus epithelium at embryonic day 17.5. Subsequent morphogenesis, including epithelial cord growth, branching, and canalization, results from concerted paracrine interactions with the stroma. A significant number of paracrine factors bind heparan sulfate (HS). We hypothesized that interfering with overall sulfation could disrupt the signaling mediated by HS-binding factors and that the undersulfated environment would allow investigation of individual exogenous morphogens. First, we investigated whether acinar morphogenesis involved HS-proteoglycan expression and found that syndecans 1 and 3 were upregulated in RWPE1 cells in the transition from two- to three-dimensional (3D) Matrigel, capable of promoting spheroid formation. We then investigated whether sodium chlorate, a general sulfation inhibitor, interfered with spheroid formation by RWPE1 cells and acinar morphogenesis in ex vivo ventral prostate (VP) organ culture. As expected, treatment with sodium chlorate inhibited spheroid formation by RWPE1 cells in 3D culture. Chlorate also inhibited ex vivo VP epithelial branching and canalization, resulting in long branchless epithelial structures. We then investigated whether the HS-binding factors, FGF10, TGF beta 1, and SDF1, could reverse the effect of sodium chlorate. Although no effect was seen in the FGF10- and TGF beta 1-treated samples, SDF1 promoted epithelial canalization in the low sulfated environment, highlighting its specific role in lumen formation. Altogether, the results show that sodium chlorate perturbed prostate morphogenesis and allowed investigation of factors involved in branching and/or canalization, implicating SDF1 signaling in epithelial canalization. (AU)

• Processo FAPESP: 12/17657-0 - Atividade da heparanase e seu papel na modulação da sinalização extracelular no desenvolvimento prostático
• Beneficiário: Guilherme Oliveira Barbosa
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 09/16150-6 - Regulação androgênica, sinalização e interações celulares no desenvolvimento, fisiologia e regressão prostática
• Beneficiário: Hernandes Faustino de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/18103-3 - Proteoglicanos de heparam sulfato na morfologia e fisiologia epitelial: knock out de Syndecan-1 usando CRISP/Cas9
• Beneficiário: Guilherme Oliveira Barbosa
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto