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TISSUE POLARITY GENE FRIZZLED IS EXPRESSED IN THE INTERSTITIAL MYOFIBROBLASTS IN A RENAL FIBROSIS.

组织极性基因卷曲在肾纤维化的间质肌成纤维细胞中表达。

基本信息

批准号：
11671051
负责人：
YOSHIMURA Ashio
金额：
$ 1.86万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671051/
关键词：
polarity gene myofibroblast renal fibrosis frizzled interstitium α-smooth muscle sctin unilateral ureteral obstruction 腎間質線維化 Myofibroblast frizzled遺伝子組織極性 in situ hybridization

项目摘要

Interstitial fibrosis is the final event of many chronic renal diseases, and the presence of myofibroblast is critical in the process. Presence of myofibroblasts (a-smooth muscle actin positive, αSMA+) is confined to a large extent to the vascular smooth muscle cells of normal kidneys but extends to the tubulointerstitium and periglomerular space in the development of fibrosis. The mechanisms that control the myofibroblast localization are unknown, but are likely to involve the transmission of polarity signals. Possible candidate genes for this control are the rat homologues of the Drosophila polarity gene frizzled. In Drosophila, the frizzled gene controls the polarity of the wing hair growth. In mammalians, two highly homologous genes (fri and fz2) have been identified. The aims of the present study were to localize and to quantify the expression of fz2 in rat kidney in the course of unilateral ureteral obstruction, in order to study their putative role in the spatial control of myofibroblast localization in interstitial fibrosis. Immunohistochemistry for αSMA and in situ hybridization for the frizzled gene fz2 are performed on serial sections at 1, 2, 3 and 5 weeks after ureteral obstruction as well as normal kidney. Gradual increase in the number of αSMA+ cells in interstitium was demonstrated from week 1 to week 5.There was no fz2+ myofibroblast in normal kidney, however it appeared in the interstitium from week 1. The peak of the number of fz2+ myofibroblast in the interstitium was shown at week 3 and it decreased at week 5 when the expansion of interstitial fibrosis was demonstrated. In conclusion, myofibroblasts express a homologue of Drosophila tissue polarity gene frizzled (fz2) and fz2 expression in myofibroblasts is involved in the spatial control of the early phase of interstitial fibrosis in a unilateral ureteral obstruction model.

间质纤维化是许多慢性肾脏疾病的最终事件，肌成纤维细胞的存在在该过程中是至关重要的。肌成纤维细胞（α-平滑肌肌动蛋白阳性，αSMA+）的存在在很大程度上局限于正常肾脏的血管平滑肌细胞，但在纤维化的发展中扩展到肾小管间质和肾小球周围间隙。控制肌成纤维细胞定位的机制尚不清楚，但可能涉及极性信号的传递。这种控制的可能候选基因是果蝇极性基因frizzled的大鼠同源物。在果蝇中，卷曲基因控制着翅膀毛发生长的极性。在马达加斯加人中，已经鉴定出两个高度同源的基因（fri和fz 2）。本研究的目的是定位和定量的表达fz 2在大鼠肾脏单侧输尿管梗阻的过程中，以研究其在间质纤维化的肌成纤维细胞定位的空间控制的假定作用。分别于输尿管梗阻后1、2、3、5周及正常肾组织连续切片进行αSMA免疫组织化学染色和fz 2基因原位杂交。从第1 ~ 5周肾组织中αSMA+细胞逐渐增多，正常肾组织中无fz 2+肌成纤维细胞，但从第1周开始肾组织中出现fz 2+肌成纤维细胞。fz 2+肌成纤维细胞在第3周达到高峰，第5周时减少，此时间质纤维化扩大。总之，肌成纤维细胞表达果蝇组织极性基因frizzled（fz 2）和fz 2在肌成纤维细胞中的表达的同源物参与空间控制的早期阶段间质纤维化在单侧输尿管梗阻模型。