Paracrine stimulation of vascular smooth muscle proliferation by diadenosine polyphosphates released from proximal tubule epithelial cells
Paracrine stimulation of vascular smooth muscle proliferation by diadenosine polyphosphates released from proximal tubule epithelial cells
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DOI：
10.1038/sj.ki.5002186
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发表时间：
2007-05-01
影响因子：
19.6
通讯作者：
Jankowski, J.
中科院分区：
文献类型：
--
作者：
Jankowski, V.;Karadogan, S.;Jankowski, J.
嘌呤能受体系统在调节肾脏血管和肾小管功能方面发挥着重要作用；然而，肾组织释放除ATP以外的嘌呤能激动剂的情况尚不清楚。在这项研究中，我们确定肾组织是否是二腺苷多磷酸的来源，二腺苷多磷酸与P-2X和P-2Y受体具有高亲和力。用基质辅助激光解吸电离-质谱法从猪全肾和LLC-PK1细胞系克隆细胞中分离纯化了二腺苷五磷酸和六磷酸二腺苷。两种聚磷酸盐在纳摩尔浓度下均能显著刺激大鼠胸主动脉来源的血管平滑肌细胞的增殖。嘌呤能受体拮抗剂苏拉明对聚磷酸盐的促生长特性没有显著影响。两种二腺苷多磷酸均可增强血小板衍生生长因子对血管平滑肌细胞的生长刺激作用。我们得出结论，二腺苷多磷酸是肾脏内源性嘌呤能激动剂，具有生理学和病理生理学相关性。这些上皮细胞代谢产物在连接能量供应和肾小管功能的同时具有血管调节特性。
The purinergic receptor system plays an important role in the regulation of both vascular and tubular functions within the kidney; however, the release of purinergic agonists other than ATP by renal tissue is not known. In this investigation, we determine if kidney tissue is a source of diadenosine polyphosphates, which have high affinity for the P-2X and P-2Y receptors. Both diadenosine pentaphosphate and hexaphosphate were identified by matrix- assisted laser desorption ionization-mass spectrometry in extracts purified from both whole porcine kidney and from cloned cells of the LLC-PK1 cell line. Both polyphosphates in nanomolar concentrations were found to significantly stimulate the proliferation of vascular smooth muscle cells derived from rat thoracic aortas. The purinergic-receptor antagonist, suramin, did not significantly affect the growth-stimulatory properties of the polyphosphates. The growth stimulation of vascular smooth muscle cells by platelet-derived growth factor was potentiated by both diadenosine polyphosphates. We conclude that diadenosine polyphosphates are endogenous purinergic agonists of the kidney that have physiologic and pathophysiologic relevance. These epithelial cell metabolic products have vasoregulatory properties while linking the energy supply and tubular function.