PDGF receptor-{beta} modulates metanephric mesenchyme chemotaxis induced by PDGF AA.
PDGF receptor-{beta} modulates metanephric mesenchyme chemotaxis induced by PDGF AA.
复制标题
PDGF 受体-{β} 调节 PDGF AA 诱导的后肾间充质趋化性。
DOI：
10.1152/ajprenal.90368.2008
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Abboud,HannaE
中科院分区：
文献类型：
--
作者：
Ricono,JillM;Wagner,Brent;Gorin,Yves;Arar,Mazen;Kazlauskas,Andrius;Choudhury,GoutamGhosh;Abboud,HannaE
PDGF B chain or PDGF receptor (PDGFR)-β-deficient (−/−) mice lack mesangial cells. To study responses of α- and β-receptor activation to PDGF ligands, metanephric mesenchymal cells (MMCs) were established from embryonicday E11.5wild-type (+/+) and −/− mouse embryos. PDGF BB stimulated cell migration in +/+ cells, whereas PDGF AA did not. Conversely, PDGF AA was chemotactic for −/− MMCs. The mechanism by which PDGFR-β inhibited AA-induced migration was investigated. PDGF BB, but not PDGF AA, increased intracellular Ca2+and the production of reactive oxygen species (ROS) in +/+ cells. Transfection of −/− MMCs with the wild-type β-receptor restored cell migration and ROS generation in response to PDGF BB and inhibited AA-induced migration. Inhibition of Ca2+signaling facilitated PDGF AA-induced chemotaxis in the wild-type cells. The antioxidantN-acetyl-l-cysteine (NAC) or the NADPH oxidase inhibitor diphenyleneiodonium (DPI) abolished the BB-induced increase in intracellular Ca2+concentration, suggesting that ROS act as upstream mediators of Ca2+in suppressing PDGF AA-induced migration. These data indicate that ROS and Ca2+generated by active PDGFR-β play an essential role in suppressing PDGF AA-induced migration in +/+ MMCs. During kidney development, PDGFR β-mediated ROS generation and Ca2+influx suppress PDGF AA-induced chemotaxis in metanephric mesenchyme.
