Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Department of Dermatology, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
Burns. 2024 Jun;50(5):1259-1268. doi: 10.1016/j.burns.2024.03.004. Epub 2024 Mar 5.
Keloid is a benign hyperplastic dermatosis with high recurrence rate and complex pathogenesis. There is no universally effective treatment yet. New therapies and elucidation of pathogenesis are urgently required.
To explore the function of IRE1α/XBP1 in keloid fibroblasts and to investigate the potential mechanism of artesunate in inhibiting keloid hyperplasia.
Human keloid fibroblasts (KFs) were cultured, and the expressions of XBP1 and TGF-β1 were detected by immunohistochemistry. The expression of IRE1 was interfered with through cell transfection and the effects of IRE1 interference on cell proliferation and the cell cycle were assessed using MTS, colony formation assays, and flow cytometry. Detection of the expressions of XBP1 and TGF-β1 by qRT-PCR and Western blot. Then artesunate was applied to a subset of the cells, and its effects on cell viability and the expression of related proteins using the same methods.
The IRE1α/XBP1 pathway was activated in KFs. Knocking out the gene IRE1α can inhibit the expression of TGF-β1, in addition, the cell viability and cell cycle progression of KFs were also significantly affected. After artesunate treatment, there was a remarkable reduction in cell proliferation. Meanwhile, the cell cycle of KFs treated with artesunate was blocked in G1 phase.After upregulating the expression of IRE1α and treating KFs with artesunate, both cell cycle and proliferation showed inhibitory effects, and related proteins also exhibited suppressed expression.
The IRE1α/XBP1 pathway is activated in keloid, and inhibiting the expression of this pathway can affect the cell proliferation activity. In addition, artesunate also has a significant effect on fibroblast proliferation, and the IRE1α/XBP1 pathway may participate in this process. These findings suggest that IRE1α/XBP1 signal pathway may be a potential target for scar treatment, and artesunate could also be a powerful candidate for keloid treatment.
瘢痕疙瘩是一种良性增生性皮肤病，具有高复发率和复杂的发病机制。目前还没有普遍有效的治疗方法。迫切需要新的治疗方法和发病机制的阐明。
探讨IRE1α/XBP1 在瘢痕疙瘩成纤维细胞中的作用，并探讨青蒿琥酯抑制瘢痕疙瘩增生的潜在机制。
培养人瘢痕疙瘩成纤维细胞（KFs），免疫组化检测 XBP1 和 TGF-β1 的表达。通过细胞转染干扰 IRE1 的表达，采用 MTS、集落形成实验和流式细胞术评估 IRE1 干扰对细胞增殖和细胞周期的影响。qRT-PCR 和 Western blot 检测 XBP1 和 TGF-β1 的表达。然后用青蒿琥酯处理一部分细胞，用同样的方法检测细胞活力和相关蛋白的表达。
IRE1α/XBP1 通路在 KFs 中被激活。敲除 IRE1α 基因可抑制 TGF-β1 的表达，此外，KFs 的细胞活力和细胞周期进程也受到显著影响。青蒿琥酯处理后，细胞增殖明显减少。同时，青蒿琥酯处理的 KFs 细胞周期被阻滞在 G1 期。上调 IRE1α 的表达并用青蒿琥酯处理 KFs 后，细胞周期和增殖均表现出抑制作用，相关蛋白的表达也受到抑制。
IRE1α/XBP1 通路在瘢痕疙瘩中被激活，抑制该通路的表达可影响细胞增殖活性。此外，青蒿琥酯对成纤维细胞增殖也有显著作用，IRE1α/XBP1 通路可能参与这一过程。这些发现表明 IRE1α/XBP1 信号通路可能是瘢痕治疗的潜在靶点，青蒿琥酯也可能是瘢痕疙瘩治疗的有力候选药物。
