Department of Dermatology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China; Shandong First Medical University, Jinan 250117, Shandong, China.
Department of Dermatology, Affiliated Hospital of Shandong University of traditional Chinese Medicine, Jinan 250012, Shandong, China.
Acta Histochem. 2023 Feb;125(2):152010. doi: 10.1016/j.acthis.2023.152010. Epub 2023 Feb 2.
Vohwinkel syndrome (VS) is a very rare autosomal dominant disorder that can cause disability and deformity in severe cases. Mutations of the LOR (loricrin) and GJB2 (Cx26) genes have been found in VS so far. Many studies have indicated that the differentiation and growth of epidermal keratinocytes are regulated by mutant Cx26, and it may explain the pathogenesis of VS. It has been found that transforming growth factor β1 (TGF-β1) expression was lower in G130V (OE1) and D66H (OE2) mutant keratinocytes in the VS model with GJB2 mutation as compared to normal keratinocytes (NC). TGF-β is a cytokine involved in the regulation of processes like cell proliferation and differentiation in different types of cells. At present, many in vitro studies focus on TGF- β 1 inhibition of keratinocyte growth.However, the relationship between TGF-β1 and VS remains unknown. This study aimed at elucidating the role and potential pathogenic mechanism of TGF-β in VS. The results indicated that the down-regulation expression of TGF-β1 in VS was linked to cell proliferation inhibition through p-Smad3/c-myc. In contrast, low-dose TGF-β1 treatment of VS keratinocytes can improve their proliferation inhibition and up-regulate the expression Cyclin D1. This suggests that low doses of TGF-β1 can improve the proliferation of VS and provide new insights into its treatment.
Vohwinkel 综合征（VS）是一种非常罕见的常染色体显性遗传疾病，在严重情况下会导致残疾和畸形。到目前为止，已经在 VS 中发现了 LOR（兜甲蛋白）和 GJB2（Cx26）基因的突变。许多研究表明，突变型 Cx26 调节表皮角质形成细胞的分化和生长，这可能解释了 VS 的发病机制。已经发现，与正常角质形成细胞（NC）相比，GJB2 突变 VS 模型中的 G130V（OE1）和 D66H（OE2）突变角质形成细胞中转化生长因子β1（TGF-β1）的表达较低。TGF-β 是一种参与调节不同类型细胞中细胞增殖和分化等过程的细胞因子。目前，许多体外研究集中在 TGF-β1 抑制角质形成细胞生长上。然而，TGF-β1 与 VS 之间的关系尚不清楚。本研究旨在阐明 TGF-β 在 VS 中的作用及其潜在的发病机制。结果表明，VS 中 TGF-β1 的下调表达与通过 p-Smad3/c-myc 抑制细胞增殖有关。相比之下，低剂量 TGF-β1 处理 VS 角质形成细胞可以改善其增殖抑制作用，并上调 Cyclin D1 的表达。这表明低剂量 TGF-β1 可以改善 VS 的增殖，并为其治疗提供新的思路。
