Fibroblast dynamics to mitigate tissue damage (B06)

该项目将确定影响间质血管室损伤反应的心脏成纤维细胞（CFs）的细胞因子和生长因子信号。我们已经确定了一种新的CFs谱系，它位于外膜并被LepR-Cre标记。在基线时，这种CF亚群是罕见的，但在心肌梗死后扩展到产生大多数疤痕成纤维细胞。我们将测试LepR-Cre+ CFs是否是组织驻留的成纤维细胞祖细胞，并探索瘦素信号在其激活中的作用。此外，我们将进行离体研究，评估（预）增殖CFs表达的一组细胞因子对自分泌和旁分泌（对内皮细胞和免疫细胞）的影响。

The project will identify cytokines and growth factors signalling to and from cardiac fibroblasts (CFs) which influence the damage response of the stroma vascular compartment. We have identified a novel lineage of CFs residing in the adventitia and labelled by LepR-Cre. At baseline, this CF subset is rare, but expands to produce the majority of scar fibroblasts after myocardial infarction. We will test whether LepR-Cre+ CFs are tissue-resident fibroblast progenitors and explore the role of leptin signalling on their activation. In addition, we will conduct ex vivo studies assessing autocrine and paracrine (on endothelial and immune cells) effects of a set of cytokines expressed by (pre)proliferative CFs.