Effects of transforming growth factor on the developing embryonic ureter: An in-vitro megaureter model in mice

详细信息    查看全文

• 作者：E. Ozturk^a ; ^{ozturkerdem583@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; O. Telli^b ; M.I. Gokce^a ; C. Ozcan^a ; T.M. Okutucu^a ; T. Soygur^b ; B. Burgu^b
• 关键词：Megaureter ; Transforming growth factor ; Mice ; Embryo
• 刊名：Journal of Pediatric Urology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：12
• 期：5
• 页码：310.e1-310.e4
• 全文大小：855 K

文摘

It is generally agreed that the cause of a megaureter is narrowing at the vesicoureteral junction, with a functional obstruction arising from an aperistaltic, juxtavesical segment that is unable to transport urine at an acceptable rate. Histological examinations of megaureter specimens have reported several histological analyses, and the pathogenic role of transforming growth factor is still a matter of speculation.

Objective

To evaluate whether transforming growth factor-beta (TGF-β) and its receptors (TGFRs) are expressed during ureterovesical junction (UVJ) and lower ureter development in mice, and whether exogenous TGF-β might postpone the maturation of smooth muscle cells, in the pathogenesis of megaureter using an embryonic organ-culture model.

Methods

Expression of TGF-β and TGFRs on the lower ureter and UVJ were determined at different embryonic days (E) (E16, 18, 20 and postnatal day 1). The functional studies were performed by harvesting ureters from wild-type mice at embryonic day 16 (E16), which were grown in serum-free organ-culture; some cultures were supplemented with TGF-β (2 and 20 ng/ml) and/or with soluble TGFR, which blocks bioactivity. Organs were harvested after 6 days and the expression of CD31 and Ki67 were assessed using immunohistochemistry. The muscle content of the UVJ and ureter were analyzed by flowcytometry.

Results

The TGF-β and TGFR positive cells were immune detected in embryonic ureters. The TGF-β expression was highest on E18 and decreased postnatally. Exogenous TGF-β decreased ureterovesical (UV) muscle differentiation and proliferation. The longitudinal muscle fibers were significantly less in TGF-β explants. The TGF-β also decreased the proportions of cells expressing α smooth muscle actin (α-SMA). Soluble TGFR blocked the effects of exogenous TGF-β.

Conclusions

In organ culture, exogenous TGF-β postpones the UV smooth muscle proliferation and affects the muscular structure. Whether the effects of TGF-β are direct or indirect, these form an in-vitro megaureter model. The finding that TGF-β is highest in embryonic ureters in vivo and decreased postnatally suggests that a pathological persistence might potentially explain the pathogenesis of primary megaureters.