TGF-ß1 stimulates movement of renal proximal tubular epithelial cells in a three-dimensional cell culture via an autocrine TGF-ß2 production.
Exp Cell Res
; 350(1): 132-139, 2017 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-27880866
ABSTRACT
TGF-ßs are multifunctional cytokines, but their roles in human renal homeostasis are not fully understood. This study investigated the role of TGF-ß1 in the movement of human renal proximal tubular epithelial cells (PTECs) in a three-dimensional (3D) model. HKC-8 cells, a human PTEC line, were grown in a 3D collagen culture system. Cell movement was observed under a microscope. The gene expression was examined using PCR Arrays or qRT-PCR, and protein levels by Western blot. Here, we showed that the tight junction structure formed between adjacent cells of a HKC-8 cell colony in 3D cultures, and TGF-ß1 stimulated their movement, evidenced by the appearance of fingerlike pseudopodia in the leader cells at the edge of the colonies. The cell movement of these human PTECs was correlated with up-regulation of both MMP2 and MMP9 and down-regulation or inactivation of PLAUR and PTK2B. Analysis of TGF-ß signaling targets confirmed autocrine production of TGF-ß2 and its cleaving enzyme furin as well as SNAI1 by TGF-ß1stimulation. Knockdown of TGF-ß2 expression disrupted TGF-ß1-stimulated PTEC invasiveness, which was correlated with the down-regulation of MMP2 and MMP9. In conclusion, the activation of TGF-ß receptor autocrine signaling by up-regulated TGF-ß2 may play a pivotal role in TGF-ß1-induced human PTEC movement, which could be mediated at least by both MMP2 and MMP9.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Movimento Celular
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Células Epiteliais
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Fator de Crescimento Transformador beta1
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Fator de Crescimento Transformador beta2
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Túbulos Renais Proximais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Ano de publicação:
2017
Tipo de documento:
Article