Dataset Information

Enhancement of HGF-induced tubulogenesis by endothelial cell-derived GDNF.

ABSTRACT: Tubulogenesis, the organization of epithelial cells into tubular structures, is an essential step during renal organogenesis as well as during the regeneration process of renal tubules after injury. In the present study, endothelial cell-derived factors that modulate tubule formation were examined using an in vitro human tubulogenesis system. When human renal proximal tubular epithelial cells (RPTECs) were cultured in gels, tubular structures with lumens were induced in the presence of hepatocyte growth factor (HGF). Aquaporin 1 was localized in the apical membrane of these tubular structures, suggesting that these structures are morphologically equivalent to renal tubules in vivo. HGF-induced tubule formation was significantly enhanced when co-cultured with human umbilical vein endothelial cells (HUVECs) or in the presence of HUVEC-conditioned medium (HUVEC-CM). Co-culture with HUVECs did not induce tubular structures in the absence of HGF. A phospho-receptor tyrosine kinase array revealed that HUVEC-CM markedly enhanced phosphorylation of Ret, glial cell-derived neurotrophic factor (GDNF) receptor, in HGF-induced tubular structures compared to those without HUVEC-CM. HUVECs produced GDNF, and RPTECs expressed both Ret and GDNF family receptor alpha1 (co-receptor). HGF-induced tubule formation was significantly enhanced by addition of GDNF. Interestingly, not only HGF but also GDNF significantly induced phosphorylation of the HGF receptor, Met. These data indicate that endothelial cell-derived GDNF potentiates the tubulogenic properties of HGF and may play a critical role in the epithelial-endothelial crosstalk during renal tubulogenesis as well as tubular regeneration after injury.

SUBMITTER: Nakasatomi M

PROVIDER: S-EPMC6405134 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Enhancement of HGF-induced tubulogenesis by endothelial cell-derived GDNF.

Nakasatomi Masao M Takahashi Shunsuke S Sakairi Toru T Ikeuchi Hidekazu H Kaneko Yoriaki Y Hiromura Keiju K Nojima Yoshihisa Y Maeshima Akito A

PloS one 20190307 3

Tubulogenesis, the organization of epithelial cells into tubular structures, is an essential step during renal organogenesis as well as during the regeneration process of renal tubules after injury. In the present study, endothelial cell-derived factors that modulate tubule formation were examined using an in vitro human tubulogenesis system. When human renal proximal tubular epithelial cells (RPTECs) were cultured in gels, tubular structures with lumens were induced in the presence of hepatocyt ...[more]

PMID: 30845150

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Dataset Information

Enhancement of HGF-induced tubulogenesis by endothelial cell-derived GDNF.

Publications

Enhancement of HGF-induced tubulogenesis by endothelial cell-derived GDNF.

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