Cordido Adrian, Vizoso-Gonzalez Marta, Nuñez-Gonzalez Laura, Molares-Vila Alberto, Chantada-Vazquez Maria Del Pilar, Bravo Susana B, Garcia-Gonzalez Miguel A
Group of Genetics and Developmental Biology of Renal Diseases, Nephrology Laboratory (N°11), Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela Clinical Hospital Complex (CHUS), 15706 Santiago de Compostela, Spain.
Genomic Medicine Group, Santiago de Compostela Clinical Hospital Complex (CHUS), 15706 Santiago de Compostela, Spain.
Biomedicines. 2022 Jan 27;10(2):290. doi: 10.3390/biomedicines10020290.
(1) Background: Polycystic liver disease (PLD) is a heterogeneous group of congenital disorders characterized by bile duct dilatation and cyst development derived from cholangiocytes. Nevertheless, the cystogenesis mechanism is currently unknown and the PLD treatment is limited to liver transplantation. Novel and efficient therapeutic approaches are th6us needed. In this context, the present work has a principal aim to find novel molecular pathways, as well as new therapeutic targets, involved in the hepatic cystogenesis process. (2) Methods: Quantitative proteomics based on SWATH-MS technology were performed comparing hepatic proteomes of and mutant/polycystic livers in a polycystic kidney disease (PKD) murine model (;). (3) Results: We identified several proteins altered in abundance, with two-fold cut-off up-regulation or down-regulation and an adjusted -value significantly related to hepatic cystogenesis. Then, we performed enrichment and a protein-protein analysis identifying a cluster focused on hepatic fibrinogens. Finally, we validated a selection of targets by RT-qPCR, and immunohistochemistry, finding a high correlation with quantitative proteomics data and validating the fibrinogen complex. (4) Conclusions: This work identified a novel molecular pathway in cystic liver disease, highlighting the fibrinogen complex as a possible new therapeutic target for PLD.
(1) 背景：多囊肝病（PLD）是一组异质性先天性疾病，其特征为胆管扩张以及源自胆管细胞的囊肿形成。然而，目前囊肿发生机制尚不清楚，且PLD的治疗局限于肝移植。因此，需要新的有效治疗方法。在此背景下，本研究的主要目的是寻找参与肝脏囊肿发生过程的新分子途径以及新治疗靶点。(2) 方法：基于SWATH-MS技术进行定量蛋白质组学分析，比较多囊肾病（PKD）小鼠模型（;）中野生型和突变型/多囊性肝脏的肝脏蛋白质组。(3) 结果：我们鉴定出了几种丰度改变的蛋白质，上调或下调两倍截断值且校正后的 值与肝脏囊肿发生显著相关。然后，我们进行了富集分析和蛋白质-蛋白质分析，确定了一个聚焦于肝脏纤维蛋白原的簇。最后，我们通过RT-qPCR、 和免疫组织化学验证了一系列靶点，发现与定量蛋白质组学数据高度相关并验证了纤维蛋白原复合物。(4) 结论：本研究确定了囊性肝病中的一条新分子途径，突出了纤维蛋白原复合物作为PLD可能的新治疗靶点。
