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ASC-J9 通过抑制 STAT3 信号通路来抑制瘢痕疙瘩成纤维细胞的增殖和细胞外基质的产生。

ASC-J9 Blocks Cell Proliferation and Extracellular Matrix Production of Keloid Fibroblasts through Inhibiting STAT3 Signaling.

机构信息

Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

International Center for Wound Repair and Regeneration (iWRR), National Cheng Kung University, Tainan 701, Taiwan.

出版信息

Int J Mol Sci. 2022 May 16;23(10):5549. doi: 10.3390/ijms23105549.

DOI:10.3390/ijms23105549
PMID:35628356
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9141592/
Abstract

Keloids are a fibrotic skin disorder caused by abnormal wound healing and featuring the activation and expansion of fibroblasts beyond the original wound margin. Signal transducer and activator of transcription 3 (STAT3) has been found to mediate the biological functions of keloid fibroblasts (KFs). Therefore, we aimed to demonstrate whether ASC-J9, an inhibitor of STAT3 phosphorylation, can suppress the activation of KFs. Western blotting results showed that ASC-J9 inhibited the levels of COL1A1 and FN1 proteins, which were upregulated in KFs, by decreasing the expression of pSTAT3 and STAT3. RNA sequencing and in vitro studies further demonstrated that ASC-J9 treatment of KFs reduced cell division, inflammation, and ROS generation, as well as extracellular matrix (ECM) synthesis. ELISA assays verified that ASC-J9 treatment significantly mitigated IL-6 protein secretion in KFs. Transmission electron microscopy images revealed that ASC-J9 induced the formation of multilamellar bodies in KFs, which is associated with autophagy-related signaling. These results suggested that inhibiting a vicious cycle of the ROS/STAT3/IL-6 axis by ASC-J9 may represent a potential therapeutic approach to suppress cell proliferation and ECM production in KFs.

摘要

瘢痕疙瘩是一种纤维性皮肤疾病，由异常的伤口愈合引起，其特征是成纤维细胞在原始伤口边缘以外的激活和扩张。信号转导子和转录激活子 3（STAT3）已被发现介导瘢痕疙瘩成纤维细胞（KFs）的生物学功能。因此，我们旨在证明 STAT3 磷酸化抑制剂 ASC-J9 是否可以抑制 KFs 的激活。Western blot 结果表明，ASC-J9 通过降低 pSTAT3 和 STAT3 的表达，抑制 COL1A1 和 FN1 蛋白在 KFs 中的上调水平。RNA 测序和体外研究进一步表明，ASC-J9 处理 KFs 可减少细胞分裂、炎症和 ROS 生成以及细胞外基质（ECM）合成。ELISA 检测证实 ASC-J9 治疗可显著减轻 KFs 中 IL-6 蛋白的分泌。透射电子显微镜图像显示，ASC-J9 诱导 KFs 中形成多层体，这与自噬相关信号有关。这些结果表明，通过 ASC-J9 抑制 ROS/STAT3/IL-6 轴的恶性循环可能代表抑制 KFs 中细胞增殖和 ECM 产生的一种潜在治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f459/9141592/546bfafc4568/ijms-23-05549-g005.jpg
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2
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3
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4
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6
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7
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8
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Scars Burn Heal. 2019 Dec 10;5:2059513119891113. doi: 10.1177/2059513119891113. eCollection 2019 Jan-Dec.
9
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10
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