کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527293 1401576 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TGF-β1 stimulates movement of renal proximal tubular epithelial cells in a three-dimensional cell culture via an autocrine TGF-β2 production
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
TGF-β1 stimulates movement of renal proximal tubular epithelial cells in a three-dimensional cell culture via an autocrine TGF-β2 production
چکیده انگلیسی


- TGF-β1 stimulates collective movement of human proximal tubular epithelial cells in 3 D cultures.
- TGF-β1-stimulated cell movement in 3 D cultures was correlated with up-regulation of TGF-β2, FURIN and MMP 2 and 9.
- Knockdown of TGF-β2 expression disrupted TGF-β1-stimulated cell movement, and resulted in downregulation of MMP2 and 9.

TGF-βs are multifunctional cytokines, but their roles in human renal homeostasis are not fully understood. This study investigated the role of TGF-β1 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-β1 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-β signaling targets confirmed autocrine production of TGF-β2 and its cleaving enzyme furin as well as SNAI1 by TGF-β1stimulation. Knockdown of TGF-β2 expression disrupted TGF-β1-stimulated PTEC invasiveness, which was correlated with the down-regulation of MMP2 and MMP9. In conclusion, the activation of TGF-β receptor autocrine signaling by up-regulated TGF-β2 may play a pivotal role in TGF-β1-induced human PTEC movement, which could be mediated at least by both MMP2 and MMP9.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 350, Issue 1, 1 January 2017, Pages 132-139
نویسندگان
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