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首页> 外文期刊>Cellular & molecular biology letters. >Leptin regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in HL-1 murine cardiomyocytes.
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Leptin regulates MMP-2, TIMP-1 and collagen synthesis via p38 MAPK in HL-1 murine cardiomyocytes.

机译：瘦素通过HL-1鼠心肌细胞中的p38 MAPK调节MMP-2，TIMP-1和胶原蛋白的合成。

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摘要

A clear association between obesity and heart failure exists and a significant role for leptin, the product of the obese gene, has been suggested. One aspect of myocardial remodeling which characterizes heart failure is a disruption in the balance of extracellular matrix synthesis and degradation. Here we investigated the effects of leptin on matrix metalloproteinase (MMP) activity, tissue inhibitor of metalloproteinase (TIMP) expression, as well as collagen synthesis in HL-1 cardiac muscle cells. Gelatin zymographic analysis of MMP activity in conditioned media showed that leptin enhanced MMP-2 activity in a dose- and time-dependent manner. Leptin is known to stimulate phosphorylation of p38 MAPK in cardiac cells and utilization of the p38 MAPK inhibitor, SB203580, demonstrated that this kinase also plays a role in regulating several extracellular matrix components, such that inhibition of p38 MAPK signaling prevented the leptin-induced increase in MMP-2 activation. We also observed that leptin enhanced collagen synthesis determined by both proline incorporation and picrosirius red staining of conditioned media. Pro-collagen type-I and pro-collagen type-III expression, measured by real-time PCR and Western blotting were also increased by leptin, effects which were again attenuated by SB203580. In summary, these results demonstrate the potential for leptin to play a role in mediating myocardial ECM remodeling and that the p38 MAPK pathway plays an important role in mediating these effects.
机译：肥胖与心力衰竭之间存在明确的联系，并且有人提出肥胖基因产物瘦素的重要作用。表征心力衰竭的心肌重塑的一个方面是细胞外基质合成和降解平衡的破坏。在这里，我们研究了瘦素对基质金属蛋白酶（MMP）活性，金属蛋白酶组织抑制剂（TIMP）表达以及HL-1心肌细胞胶原合成的影响。在条件培养基中对MMP活性的明胶酶谱分析表明，瘦素以剂量和时间依赖性方式增强MMP-2活性。已知瘦素可刺激心肌细胞中p38 MAPK的磷酸化，并利用p38 MAPK抑制剂SB203580，证明该激酶在调节细胞外基质成分中也发挥作用，从而抑制p38 MAPK信号传导可阻止瘦素诱导的增加。在MMP-2激活中。我们还观察到瘦素增强了脯氨酸的掺入和条件培养基的picrosirius红染色，从而确定了胶原蛋白的合成。通过实时PCR和Western印迹测定的I型胶原蛋白和III型胶原蛋白的表达也因瘦素而增加，SB203580再次减弱了这种作用。总之，这些结果证明了瘦素可能在介导心肌ECM重塑中发挥作用，而p38 MAPK途径在介导这些作用中起着重要作用。

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