Tsuboi Ichiro, Mitsui Yosuke, Yoshinaga Kasumi, Yamanoi Tomoaki, Sekito Takanori, Maruyama Yuki, Sadahira Takuya, Nishimura Shingo, Bekku Kensuke, Araki Motoo
Department of Urology Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan.
Department of Inflammation and Immunity, Lerner Research Institute Cleveland Clinic, Cleveland, OH, USA.
Sci Rep. 2025 Sep 26;15(1):33014. doi: 10.1038/s41598-025-18391-2.
Clinical improvement in pigmentation is frequently observed after kidney transplantation. However, the underlying molecular and histological mechanisms remain unclear. We conducted a study to quantify the skin color change using a handheld reflected light colorimeter and to investigate protein expression changes in the skin before and after kidney transplantation. Paired skin biopsies were obtained from three patients who underwent kidney transplantation before and one month after transplantation. Protein expression was analyzed using iTRAQ-based quantitative proteomics. Differentially expressed proteins were identified and visualized using hierarchical clustering and volcano plots. Histopathological evaluation included hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical (IHC) staining for keratin (KRT) 7, KRT19, and MelanA. Skin pigmentation of the arms, ankles, and abdomen had significant L-value improvement after kidney transplantation. Proteomic profiling identified 2148 proteins, with six proteins showing significant differential expression after transplantation. Among them, KRT7, KRT19, and prostaglandin D2 synthase (PTGDS) were significantly downregulated, potentially reflecting reduced epithelial stress and systemic inflammation. H&E and Masson's trichrome staining revealed a post-transplantation reduction in dermal pigmentation and collagen content. IHC showed decreased KRT7, KRT19, and MelanA expression after transplantation. Our results suggest that targeting KRT or prostaglandin pathways may offer new treatments for ESRD-related skin symptoms.
肾移植后常观察到色素沉着的临床改善。然而，其潜在的分子和组织学机制仍不清楚。我们进行了一项研究，使用手持式反射光色度计量化皮肤颜色变化，并研究肾移植前后皮肤中蛋白质表达的变化。从三名接受肾移植的患者移植前及移植后一个月获取配对的皮肤活检样本。使用基于iTRAQ的定量蛋白质组学分析蛋白质表达。使用层次聚类和火山图鉴定并可视化差异表达的蛋白质。组织病理学评估包括苏木精和伊红（H&E）染色、Masson三色染色以及对角蛋白（KRT）7、KRT19和黑色素A（MelanA）的免疫组织化学（IHC）染色。肾移植后，手臂、脚踝和腹部的皮肤色素沉着L值有显著改善。蛋白质组分析鉴定出2148种蛋白质，其中六种蛋白质在移植后显示出显著差异表达。其中，KRT7、KRT19和前列腺素D2合酶（PTGDS）显著下调，这可能反映了上皮应激和全身炎症的减轻。H&E和Masson三色染色显示移植后真皮色素沉着和胶原蛋白含量减少。IHC显示移植后KRT7、KRT19和MelanA表达降低。我们的结果表明，针对角蛋白或前列腺素途径可能为终末期肾病相关皮肤症状提供新的治疗方法。
