Pseudoxanthoma elasticum is an autosomal recessive genodermatosis with variable expression, due to mutations in the ABCC6 or ENPP1 gene. It is characterized by elastic fiber mineralization and fragmentation, resulting in skin, eye and cardiovascular symptoms. Significant advances have been made in the last 20 years with respect to the phenotypic characterization and pathophysiological mechanisms leading to elastic fiber mineralization. Nonetheless, the substrates of the ABCC6 transporter - the main cause of PXE - remain currently unknown. Though the precise mechanisms linking the ABCC6 transporter to mineralization of the extracellular matrix are unclear, several studies have looked into the cellular consequences of ABCC6 deficiency in PXE patients and/or animal models. In this paper, we compile the evidence on cellular signaling in PXE, which seems to revolve mainly around TGF-βs, BMPs and inorganic pyrophosphate signaling cascades. Where conflicting results or fragmented data are present, we address these with novel signaling data. This way, we aim to better understand the up- and down-stream signaling of TGF-βs and BMPs in PXE and we demonstrate that ANKH deficiency can be an additional mechanism contributing to decreased serum PPi levels in PXE patients.

弹性假黄瘤是一种常染色体隐性遗传性皮肤病，由于ABCC6或ENPP1中的突变而具有可变表达基因。它的特征是弹性纤维矿化和破碎，导致皮肤，眼睛和心血管症状。在过去的20年中，在导致弹性纤维矿化的表型表征和病理生理机制方面取得了重大进展。尽管如此，ABCC6转运蛋白的底物-PXE的主要原因-目前仍然未知。尽管尚不清楚将ABCC6转运蛋白与细胞外基质矿化联系起来的确切机制，但有几项研究调查了PXE患者和/或动物模型中ABCC6缺乏的细胞后果。在本文中，我们收集了有关PXE中细胞信号传导的证据，该证据似乎主要围绕TGF-β，BMP和无机焦磷酸盐信号传导级联旋转。如果存在冲突的结果或数据碎片，我们将使用新颖的信号数据来解决这些问题。这样，我们旨在更好地了解PXE中TGF-β和BMP的上游和下游信号传导，并证明ANKH缺乏可能是导致PXE患者血清PPi水平降低的另一种机制。