Angiotensin II stimulates Pax-2 in rat kidney proximal tubular cells: impact on proliferation and apoptosis.
Angiotensin II stimulates Pax-2 in rat kidney proximal tubular cells: impact on proliferation and apoptosis.
复制标题
血管紧张素 II 刺激大鼠肾近端肾小管细胞中的 Pax-2：对增殖和凋亡的影响。
DOI：
10.1111/j.1523-1755.2004.66008.x
复制
发表时间：
2004
影响因子：
19.6
通讯作者：
Ingelfinger,JulieR
中科院分区：
文献类型：
--
作者：
Zhang,Shao-Ling;Guo,Jun;Moini,Babak;Ingelfinger,JulieR
血管紧张素 II 刺激大鼠肾近端肾小管细胞中的 Pax-2：对增殖和凋亡的影响。背景肾内肾素-血管紧张素系统 (RAS) 密切参与肾损伤后发生的肾小管细胞增殖、凋亡和再生。虽然肾小管血管紧张素 II (Ang II) 2 型受体 (AT2R) 在出生后大大减少，但在受伤后其数量会增加。值得注意的是，在损伤恢复过程中，肾小管细胞表现出相对不成熟的表型，表达参与肾单位发育的基因，例如配对同源框-2基因（Pax-2）。本研究假设 AT2R 激活会刺激永生化大鼠肾近端肾小管细胞 (IRPTC) 中的 Pax-2 基因表达，正如我们在胎儿细胞中发现的那样。分别通过末端转移酶介导的脱氧尿苷三磷酸 (dUTP) 缺口末端标记 (TUNEL) 测定和溴脱氧尿苷 (BrdU) 掺入分析具有 Pax-2 有义和反义方向的稳定 IRPTC 转化子的细胞凋亡和增殖。 结果 Ang II 通过 AT2R 上调 IRPTC 中的 Pax-2 基因表达。 Ang II 对 Pax-2 基因表达的刺激作用可被 PD123319（AT2R 抑制剂）、AG 490（特异性 Janus 激酶 2 (JAK2) 抑制剂）和金雀异黄素（酪氨酸激酶抑制剂）阻断，但不能被氯沙坦（AT1R 抑制剂）阻断。稳定转染有义Pax-2 cDNA上调Pax-2表达，而反义Pax-2 cDNA下调Pax-2表达。结论我们的研究表明Ang II通过AT2R和JAK2/信号转导子和转录激活子(STAT)信号转导通路刺激IRPTC中Pax-2基因表达，这可能在损伤后的肾脏修复中发挥重要作用。缺乏 Pax-2 基因表达的细胞似乎更容易凋亡而不是增殖。
Angiotensin II stimulates Pax-2 in rat kidney proximal tubular cells: Impact on proliferation and apoptosis.BackgroundThe intrarenal renin-angiotensin system (RAS) is intimately involved in the tubular cell proliferation, apoptosis and regeneration that occur following renal injury. Though tubular angiotensin II (Ang II) type 2 receptors (AT2R) decrease greatly after birth, their number increases after injury. Notably, during recovery from injury, renal tubular cells display a relatively immature phenotype expressing genes that are involved in nephron development, for example, the paired homeobox-2 gene (Pax-2). The present investigation hypothesized that AT2R activation would stimulate Pax-2 gene expression in immortalized rat renal proximal tubular cells (IRPTC), as we have found in fetal cells.MethodsPax-2 gene expression in IRPTC was evaluated by immunofluorescence, Western blot, reverse transcription-polymerase chain reaction (RT-PCR) with or without Ang II treatment; apoptosis and proliferation were analyzed by terminal transferase-mediated deoxyuridine triphosphate (dUTP) nick end-labeling (TUNEL) assay and bromodeoxyuridine (BrdU) incorporation in stable IRPTC transformants with Pax-2 sense and antisense orientation, respectively.ResultsAng II up-regulated Pax-2 gene expression via AT2R in IRPTC. The stimulatory effect of both Ang II on Pax-2 gene expression was blocked by PD123319 (AT2R inhibitor), AG 490 (specific Janus kinase 2 (JAK2) inhibitor) and genistein (tyrosine kinase inhibitor), but not by losartan (AT1R inhibitor). Stable transfection of sense Pax-2 cDNA increased, whereas antisense Pax-2 cDNA down-regulated Pax-2 expression.ConclusionOur studies suggest that Ang II stimulates Pax-2 gene expression in IRPTC via AT2R and the JAK2/signal transducers and activators of transcription (STAT) signaling transduction pathway, which may be important in renal repair following injury. Cells lacking Pax-2 gene expression appear to be prone toward apoptosis rather than proliferation.