The role of SDF1 in prostate epithelial morphogenesis

Author(s)

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

Affiliation

^[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

• Document type: Journal article
• Source: Journal of Cellular Physiology; v. 234, n. 5, p. 6886-6897, MAY 2019.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 12/17657-0 - Heparanase activity and its role in the modulation of extracellular signaling in prostate development
• Grantee: Guilherme Oliveira Barbosa
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 09/16150-6 - Androgen regulation, sinalization and cellular interactions in prostate development, physiology and regression
• Grantee: Hernandes Faustino de Carvalho
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/18103-3 - Heparan sulfate proteoglycans in epithelial morphogenesis and physiology: knock out of Syndecan-1 using CRISPR-Cas9
• Grantee: Guilherme Oliveira Barbosa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)