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TGF-β1/Smads/α-SMA 通路的激活与神经源性膀胱患儿的组织学和功能变化有关。

Activation of the TGF-β1/Smads/α-SMA pathway is related to histological and functional changes in children with neurogenic bladder.

机构信息

Department of Pediatric Urodynamic Center, Henan Joint International Pediatric Urodynamic Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Henan Joint International Pediatric Urodynamic Laboratory, Zhengzhou, China.

出版信息

Sci Rep. 2022 Jun 3;12(1):9285. doi: 10.1038/s41598-022-13470-0.

Abstract

This research is to investigate the expression of the TGF-β1/Smads/α-SMA pathway and its effect on bladder histology and function in children with neurogenic bladder (NB). The bladder specimens from 10 children with NB and 8 children with vesicoureteral junction obstruction were collected into the NB and control groups. The expression of TGF-β1, Smad2, Smad3, Smad4, Smad6, α-SMA, fibronectin, collagen I and collagen III in bladder tissues was detected. In addition, the histological characteristics of the bladder were evaluated. A preoperative urodynamic study was performed on all children with NB. We analysed the correlations among the expression of the marker protein a-SMA in myofibroblasts, effector cells of the pathway, and bladder function parameters. Compared with those in the control group, the expression of TGF-β1, Smad2, Smad3, Smad4, α-SMA, fibronectin, collagen I and collagen III was significantly increased in the NB group, while the expression of Smad6 was decreased (p < 0.01). HE and Masson staining in the NB group showed increased collagen levels and hypertrophy of smooth muscle cells. Children with NB had a low bladder volume ratio (BVR), low compliance (△C) and high maximum bladder pressure, low maximum flow rate, large postvoid residual volume, low bladder contraction index and low bladder voiding efficiency. The expression of α-SMA was negatively correlated with the BVR (r =  - 0.7066, P = 0.0223) and △C (r =  - 0.6516, P = 0.0412). We conclude that the TGF-β1/Smads/α-SMA pathway is activated in the bladder tissue of children with NB and may be involved in the processes causing histological and functional changes.

摘要

本研究旨在探讨 TGF-β1/Smads/α-SMA 通路的表达及其对神经源性膀胱(NB)患儿膀胱组织学和功能的影响。收集 10 例 NB 患儿和 8 例膀胱输尿管反流梗阻患儿的膀胱标本,分为 NB 组和对照组。检测膀胱组织中 TGF-β1、Smad2、Smad3、Smad4、Smad6、α-SMA、纤维连接蛋白、I 型胶原和 III 型胶原的表达,并对膀胱组织的组织学特征进行评价。所有 NB 患儿均进行术前尿动力学研究,分析肌成纤维细胞标志蛋白α-SMA 的表达与通路效应细胞及膀胱功能参数的相关性。与对照组相比,NB 组 TGF-β1、Smad2、Smad3、Smad4、α-SMA、纤维连接蛋白、I 型胶原和 III 型胶原表达明显增加,Smad6 表达降低(p<0.01)。NB 组 HE 和 Masson 染色显示胶原水平升高,平滑肌细胞肥大。NB 患儿膀胱容量比(BVR)低、顺应性(△C)低、最大膀胱压高、最大尿流率低、残余尿量多、膀胱收缩指数低、膀胱排空效率低。α-SMA 的表达与 BVR(r=-0.7066,P=0.0223)和△C(r=-0.6516,P=0.0412)呈负相关。综上,TGF-β1/Smads/α-SMA 通路在 NB 患儿的膀胱组织中被激活,可能参与引起组织学和功能变化的过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/71b4/9166803/d57a4b4f202e/41598_2022_13470_Fig1_HTML.jpg

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