EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA ON CARDIAC CELLS

转化生长因子-β的三种同种型先前已被发现。 与心脏的胚胎发育有关， 缺血/再灌注损伤后的心肌损害。 TGF-β 1具有 被定位于细胞内的线粒体和收缩丝 的心肌细胞，这表明在心肌的内在作用。 到 为了确定心脏保护的机制，我们进行了 新的研究基于对TGF-β和 炎症介质如白细胞介素-1，肿瘤坏死因子， 干扰素γ和内毒素对培养新生儿心脏 肌细胞 我们已经证明外源性TGF-β稳定了 这些心肌细胞在成纤维细胞基质上培养的速率， 它们在无血清培养基中自发的有节奏的跳动。 此外，使用 阻断TGF-β抗体，我们已经证明内源性TGF-β 由这些肌细胞分泌的蛋白质以自分泌方式起作用，以维持它们的 打浆率 相反，白细胞介素-1 β，一种炎症介质， 在心肌损伤时由免疫细胞分泌，抑制心肌细胞的跳动。 而TGF-β可以克服这种抑制作用。 的 TGF-β和IL-1的拮抗作用没有观察到， 与天然成纤维细胞相比，肌细胞在明胶上培养 矩阵 这些数据表明，TGF-β是一种重要的调节因子， 心脏的收缩功能， 了解健康和疾病中的心脏生理学。

The three isoforms of transforming growth factor-beta have previously been implicated in embryonic development of the heart as well as in repair of myocardial damage following ischemia/reperfusion injury. TGF-Beta 1 has been localized intracellularly to mitochondria and contractile filaments of cardiac myocytes, suggesting an intrinsic role in the myocardium. To attempt to identify the mechanisms of cardioprotection, we have undertaken new studies based on examination of the effects of TGF-Beta and of inflammatory mediators such as interleukin-1, tumor necrosis factor, interferon gamma, as well as endotoxin, on cultured neonatal cardiac myocytes. We have shown that exogenous TGF-Beta stabilizes the beating rate of these cardiac myocytes cultured on fibroblast matrix, and sustains their spontaneous rhythmic beating in serum-free medium. Moreover, using blocking antibodies to TGF-Beta, we have shown that endogenous TGF-Beta secreted by these myocytes acts in an autocrine fashion to maintain their beating rate. In contrast, interleukin-1 Beta, an inflammatory mediator secreted by immune cells during myocardial injury, inhibits the beating of cardiac myocytes, and TGF-Beta can overcome this inhibition. The antagonistic effects of TGF-Beta and IL-1 were not observed when the myocytes were cultured on gelatin, as compared to native fibroblast matrix. The data indicate that TGF-Beta is an important regulator of contractile function of the heart and have significant implications for understanding cardiac physiology in both health and disease.