细胞科学与治疗杂志
开放获取

抽象的

OSM 刺激的心肌细胞释放 FGF23 C 端片段

Ranganath Maringanti、Thomas Kubin、Ayse Cetinkaya、Markus Schönburg、Andres Beiras- Fernandez、Thomas Braun、Thomas Walther、Sawa Kostin 和 Manfred Richter

背景：最近的研究强调 FGF23 增加与心脏病发病机制的相关性。尽管人们普遍认为骨骼而不是心脏是 FGF23 的主要来源，但我们之前证明制瘤素 M (OSM) 激活的心肌细胞强烈分泌 FGF23。该磷酸钙可以作为完整分子 (iFGF23) 以及 C 端 (cFGF23) 和 N 端 (nFGF23) 片段释放。由于裂解不仅使 iFGF23 失活，而且还可能发挥拮抗活性，我们想确定心肌细胞分泌哪种形式。

Methods: Adult cultured cardiomyocytes were stimulated with OSM or albumin as control. Supernatant and cell lysate were analyzed by Western blot (WB) and specific ELISAs against cFGF23 as well as iFGF23. Expression of FGF23 in cardiomyocytes of 6 patients with coronary heart diseases (CHD) was analyzed by confocal microscopy because OSM signaling cascades are activated after myocardial infarction.

Results: WB analysis identified cFGF23 as well as nFGF23 while iFGF23 was hardly detectable in the supernatant of OSM-stimulated cardiomyocytes. Analysis of the supernatant by ELISAs revealed that less than 3% of this secreted phosphatonin was intact. In patients with CHD the number of FGF23 positive cardiomyocytes increased from 0.2% in the remote zone to 4.4% in the border zone.

结论：心肌细胞表达和释放 FGF23 表明局部和全身功能。iFGF23/cFGF23 比率的测定对于了解这种生长因子在心脏病患者中的功能作用至关重要。