HCaRG increases renal cell migration by a TGF-α autocrine loop mechanism
HCaRG increases renal cell migration by a TGF-α autocrine loop mechanism
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DOI：
10.1152/ajprenal.00103.2005
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发表时间：
2005-12-01
影响因子：
4.2
通讯作者：
Tremblay, J
中科院分区：
文献类型：
--
作者：
El Hader, C;Tremblay, S;Tremblay, J
我们以前已经表明，高血压相关的钙调节基因（HCaRG）参与肾细胞增殖和分化的控制（DevlinAM，SolbanN，TremblayS，GutkowskaJ，SchmblayW，奥尔洛夫SN，LewanczukR，HametP，和TremblayJ.AmJPhysiolRenalPhysiol284：F753 - F762，2003）.为了确定HCaRG是否在损伤后的肾修复中起作用，我们通过比较单独用质粒或用含有HCaRG cDNA的质粒稳定转染的两种肾细胞系[HEK 293和Madin-Darby犬肾（MDCK）- C7]的细胞迁移来扩展我们对HCaRG的细胞功能的研究。表达HCaRG的HEK 293细胞增殖较低，迁移速度比对照细胞快，对细胞外基质的粘附性更强。在MDCK-C7细胞稳定转染HCaRG cDNA后，也观察到更快的迁移。HCaRG过表达诱导HEK 293细胞的主要形态学变化，包括板状伪足的形成。表达HCaRG的HEK 293细胞的表达微阵列揭示了已知参与细胞迁移和板状伪足形成的几个基因的表达升高，包括转化生长因子-α（TGF-α）、半乳糖凝集素、自分泌运动因子和纤连蛋白。这些细胞表现出增强的活化TGF-α的合成和释放。来自HCaRG表达细胞的条件培养基刺激了对照细胞的迁移并诱导了显著的形态学变化，部分是通过激活TFG-alpha/EGF受体。总之，这些数据支持HCaRG通过其对肾细胞迁移和TGF-α分泌的影响在损伤后肾修复中的作用。
We have shown previously that the hypertension- related, calcium- regulated gene ( HCaRG) is involved in the control of renal cell proliferation and differentiation ( Devlin AM, Solban N, Tremblay S, Gutkowska J, Schurch W, Orlov SN, Lewanczuk R, Hamet P, and Tremblay J. Am J Physiol Renal Physiol 284: F753 - F762, 2003). To determine whether HCaRG plays a role in kidney repair after injury, we extended our studies on the cellular function of HCaRG by comparing cell migration of two kidney cell lines [HEK293 and Madin-Darby canine kidney (MDCK)- C7] stably transfected with the plasmid alone or with a plasmid containing HCaRG cDNA. HCaRG-expressing HEK293 cells, which undergo lower proliferation, migrated faster than control cells and presented greater adhesiveness to the extracellular matrix. Faster migration was also observed for the MDCK-C7 cells, after they were stably transfected with HCaRG cDNA. HCaRG overexpression induced major morphological changes in HEK293 cells, including the formation of lamellipodia. Expression microarrays of HCaRG-expressing HEK293 cells revealed the elevated expression of several genes known to be involved in cell migration and lamellipodia formation, including transforming growth factor-alpha (TGF-alpha), galectins, autotaxins and fibronectin. These cells exhibited augmented synthesis and release of activated TGF-alpha. Conditioned medium from HCaRG-expressing cells stimulated the migration and induced significant morphological changes in control cells, in part, through activation of the TFG-alpha/EGF receptor. Together, these data support a role for HCaRG in kidney repair after injury through its effect on renal cell migration and TGF-alpha secretion.