Renal Research Institute, Departments of Medicine, Pharmacology and Physiology, New York Medical College at Touro University, Valhalla, New York, USA; Department of Nephrology and Rheumatology, Göttingen University Medical Center, Georg August University, Göttingen, Germany.
Renal Research Institute, Departments of Medicine, Pharmacology and Physiology, New York Medical College at Touro University, Valhalla, New York, USA; Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, South Korea.
Kidney Int. 2017 Sep;92(3):558-568. doi: 10.1016/j.kint.2017.02.033. Epub 2017 May 3.
The secretome, defined as a portion of proteins secreted by specific cells to the extracellular space, secures a proper microenvironmental niche not only for the donor cells, but also for the neighboring cells, thus maintaining tissue homeostasis. Communication via secretory products exists between endothelial cells and fibroblasts, and this local mechanism maintains the viability and density of each compartment. Endothelial dysfunction, apart from obvious cell-autonomous defects, leads to the aberrant secretome, which predisposes fibroblasts to acquire a myofibroblastic fibrogenic phenotype. In our recent profiling of the secretome of such dysfunctional profibrogenic renal microvascular endothelial cells, we identified unique profibrogenic signatures, among which we detected ligands of Notch and Wnt-β-catenin pathways. Here, we stress the role of reprogramming cues in the immediate microenvironment of (myo)fibroblasts and the contribution of the endothelial secretome to the panoply of instructive signals in the vicinity of fibroblasts. We hope that this brief overview of endothelial-fibroblast communication in health and disease will lead to eventual unbiased proteomic mapping of individual secretomes of glomerular and tubular epithelial cells, pericytes, and podocytes through reductionist approaches to allow for the synthetic creation of a complex network of secretomic signals acting as reprogramming factors on individual cell types in the kidney. Knowledge of profibrogenic and antifibrogenic signatures in the secretome may garner future therapeutic efforts.
细胞外基质被定义为特定细胞分泌到细胞外空间的蛋白质部分，它不仅为供体细胞，也为邻近细胞提供了适当的微环境龛位，从而维持组织内环境平衡。内皮细胞和成纤维细胞之间通过分泌产物进行通讯，这种局部机制维持着每个隔室的活力和密度。内皮功能障碍除了明显的细胞自主性缺陷外，还会导致异常的细胞外基质分泌，使成纤维细胞容易获得肌成纤维细胞纤维生成表型。在我们最近对这种功能失调的致纤维化肾脏微血管内皮细胞的细胞外基质进行的分析中，我们发现了独特的致纤维化特征，其中包括我们检测到的 Notch 和 Wnt-β-catenin 通路的配体。在这里，我们强调了重编程信号在（肌）成纤维细胞的即时微环境中的作用，以及内皮细胞外基质对成纤维细胞附近所有有指导意义的信号的贡献。我们希望，对健康和疾病状态下内皮细胞和成纤维细胞通讯的简要概述，将通过还原论方法最终导致肾小球和肾小管上皮细胞、周细胞和足细胞的单个细胞外基质的无偏蛋白质组学图谱的绘制，从而允许作为重编程因子的细胞外基质信号的复杂网络的合成创建，作用于肾脏中的单个细胞类型。对细胞外基质中的致纤维化和抗纤维化特征的了解可能会为未来的治疗努力提供依据。
