A型肉毒毒素作用下瘢痕成纤维细胞凋亡中 GADD153 的分子机制
The molecular mechanism of GADD153 in apoptosis of keloid fibroblasts exposed to botulinum toxin type A.
机构信息
Department of plastic surgery, Peking University Shenzhen Hospital, Shenzhen, China.
Translational Medicine Center, Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan.
出版信息
J Cell Mol Med. 2021 Oct;25(19):9402-9410. doi: 10.1111/jcmm.16881. Epub 2021 Sep 2.
Apoptosis plays a key role in keloids. Growth arrest and DNA damage-inducible gene 153 (GADD153) is regulated by apoptosis. Botulinum toxin type A (BTXA) can induce apoptosis in keloid fibroblasts. This research aimed to explore the hypothesis that GADD153 mediates apoptosis in keloid fibroblasts exposed to BTXA. BTXA significantly induced GADD153 protein and mRNA expression in keloid fibroblasts. Treatment with c-Jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and tumour necrosis factor-alpha (TNF-α) antibodies reversed the BTXA-induced GADD153 expression. BTXA enhanced the transcriptional activity of GADD153, whereas the GADD153 mutant plasmid, JNK siRNA and anti-TNF-α antibody treatment abolished the BTXA-induced transcriptional activity of GADD153. The addition of TNF-α to keloid fibroblasts markedly increased GADD153 protein expression. The addition of GADD153 siRNA, SP600125 and anti-TNF-α antibodies reversed cell death and caspase 3 and 9 activity induced by BTXA.
细胞凋亡在瘢痕疙瘩中起关键作用。生长停滞和 DNA 损伤诱导基因 153（GADD153）受细胞凋亡调控。肉毒杆菌毒素 A（BTXA）可诱导瘢痕疙瘩成纤维细胞凋亡。本研究旨在探讨 BTXA 作用于瘢痕疙瘩成纤维细胞时 GADD153 是否介导细胞凋亡。BTXA 可显著诱导瘢痕疙瘩成纤维细胞中 GADD153 蛋白和 mRNA 的表达。用 c-Jun N 端激酶（JNK）抑制剂 SP600125、JNK 小干扰 RNA（siRNA）和肿瘤坏死因子-α（TNF-α）抗体处理后，BTXA 诱导的 GADD153 表达被逆转。BTXA 增强了 GADD153 的转录活性，而 GADD153 突变质粒、JNK siRNA 和抗 TNF-α 抗体处理则消除了 BTXA 诱导的 GADD153 转录活性。TNF-α 加入瘢痕疙瘩成纤维细胞中可显著增加 GADD153 蛋白表达。加入 GADD153 siRNA、SP600125 和抗 TNF-α 抗体可逆转 BTXA 诱导的细胞死亡和 caspase 3、9 活性。
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