Loss of Bicc1 impairs tubulomorphogenesis of cultured IMCD cells by disrupting E-cadherin-based cell-cell adhesion.
Loss of Bicc1 impairs tubulomorphogenesis of cultured IMCD cells by disrupting E-cadherin-based cell-cell adhesion.
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DOI：
10.1016/j.ejcb.2010.01.002
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发表时间：
2010-06
影响因子：
6.6
通讯作者：
Wu, Guanqing
中科院分区：
文献类型：
--
作者：
Fu, Yulong;Kim, Ingyu;Lian, Peiwen;Li, Ao;Zhou, Liang;Li, Cunxi;Liang, Dan;Coffey, Robert J.;Ma, Jie;Zhao, Ping;Zhan, Qimin;Wu, Guanqing
Bicaudal-C（Bic-C）基因最初在果蝇中发现。基因产物Bic-C被认为是在转录后水平靶向不同蛋白质的RNA结合分子。最近的研究表明，这个基因在许多物种中是保守的，从秀丽隐杆线虫到人类。这种蛋白质的破坏可以干扰果蝇卵母细胞前卵泡细胞的正常迁移方向，而小鼠Bicc 1（Bic-C的小鼠同源物）的突变导致模仿人类遗传性多囊肾病（PKD）的表型。然而，Bicc 1基因产物在哺乳动物系统中的细胞功能在很大程度上仍然未知。在本研究中，我们建立了稳定的IMCD（小鼠内髓集合管）细胞系，其中Bicc 1沉默短发夹RNA抑制（shRNA）。我们发现，抑制Bicc 1破坏了正常的小管形态发生，并诱导三维培养中生长的IMCD细胞的囊形成。为了确定是什么因素导致了这种缺陷，我们系统地研究了Bicc 1沉默的IMCD细胞的生物学变化。我们发现，细胞有显着的缺陷，在E-钙粘蛋白为基础的细胞-细胞粘附，沿着肌动蛋白细胞骨架组织，细胞-细胞外基质相互作用，细胞增殖和凋亡的异常。这些发现表明，缺乏Bicc 1导致正常细胞-细胞连接的破坏，这反过来又阻碍了上皮极性的建立。这些细胞缺陷可能引发体外生长的IMCD细胞的异常小管形态发生和囊形成。在Bicc 1沉默的IMCD细胞中观察异常细胞行为揭示了Bicc 1在肾上皮细胞中的功能，并为多囊肾病的潜在致病机制提供了见解。
Bicaudal-C (Bic-C) gene was originally discovered in Drosophila melanogaster. The gene product Bic-C is thought to serve as an RNA-binding molecule targeting diverse proteins at the post-transcriptional level. Recent research has shown this gene to be conserved in many species, from Caenorhabditis elegans to humans. Disruption of this protein can disturb the normal migration direction of the anterior follicle cell of Drosophila oocytes, while mutation of a mouse Bicc1 (a mouse homologue of Bic-C) results in phenotypes mimicking human hereditary polycystic kidney disease (PKD). However, the cellular function of Bicc1 gene products in mammalian system remains largely unknown. In this study, we established stable IMCD (mouse inner medullary collecting duct) cell lines, in which Bicc1 was silenced by short hairpin RNA inhibition (shRNA). We show that inhibition of Bicc1 disrupted normal tubulomorphogenesis and induced cystogenesis of IMCD cells grown in three dimensional cultures. To determine what factors contributed to the defect, we systematically examined biological changes of Bicc1-silenced IMCD cells. We found that the cells had significant defects in E-cadherin-based cell-cell adhesion, along with abnormalities in actin cytoskeleton organization, cell-extracellular matrix interactions, cell proliferation, and apoptosis. These findings suggest that lack of Bicc1 leads to disruption of normal cell-cell junctions, which in turn impedes establishment of epithelial polarity. These cellular defects may initiate abnormal tubulomorphogenesis and cystogenesis of IMCD cells grown in vitro. The observation of aberrant cellular behaviors in Bicc1-silenced IMCD cells reveal functions for Bicc1 in renal epithelial cells and provides insight into a potential pathogenic mechanism of polycystic kidney disease.
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影响因子：
56.9
作者：
Mochizuki, T;Wu, GQ;Somlo, S
通讯作者：
Somlo, S
DOI：
10.1152/ajprenal.00015.2004
发表时间：
2004-10-01
影响因子：
4.2
作者：
Chen, D;Roberts, R;Zent, R
通讯作者：
Zent, R
影响因子：
5.3
作者：
Chen, TP;Damaj, BB;Richard, S
通讯作者：
Richard, S
影响因子：
2.5
作者：
Cogswell, C;Price, SJ;Bryda, EC
通讯作者：
Bryda, EC
影响因子：
--
作者：
Bouvrette, Denise J.;Price, Sarah J.;Bryda, Elizabeth C.
通讯作者：
Bryda, Elizabeth C.