Huang Rong, Han Bing, Peng Jianzhong, Jiao Hu
Department of Dermatology, Hangzhou Third People's Hospital, 38, West Lake Avenue, Hangzhou, 310009, Zhejiang, China.
Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33 Ba-Da-Chu Road, Beijing, 100144, China.
Aesthetic Plast Surg. 2025 Feb;49(3):897-907. doi: 10.1007/s00266-024-04375-6. Epub 2024 Oct 14.
Keloid disease is a chronic fibroproliferative disease that occurs after tissue injury, and the currently available treatments are unsatisfactory.
We aimed to explore the level of autophagy in keloid fibroblasts (KFbs) and adjacent normal fibroblasts (NFbs). In addition, whether polypyrimidine tract-binding protein (PTB) regulates the biological functions of KFbs via autophagy was also investigated.
The morphology of fibroblasts in normal skin and keloids was observed transmission electron microscopy. We silenced PTB with PTB-specific siRNA to determine whether PTB-regulated KFb proliferation. Acridine orange and LysoTracker Red staining was performed to label acidic compartments. Interestingly, when autophagy was inhibited by wortmannin, the PTB knockdown-mediated decrease in KFb migration and proliferation was abolished, while the collagen I and III levels were not altered; these results indicated that PTB regulated the migration and proliferation of KFbs via autophagy, while collagen synthesis occurred independently of PTB regulation.
Many activities related to the survival and function of KFbs are controlled by PTB. Transmission electron microscopy revealed more autophagosomes and autolysosomes in KFbs than in NFbs. PTB induced autophagy in KFbs, as demonstrated by the significantly greater number of autophagosomes in KFbs after PTB knockdown, which was revealed by acridine orange and LysoTracker staining.
Our study is the first to show that PTB regulates the migration and proliferation of KFbs via autophagy and that PTB regulates collagen synthesis in KFbs in an autophagy-independent manner.
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瘢痕疙瘩是一种在组织损伤后发生的慢性纤维增生性疾病，目前可用的治疗方法并不理想。
我们旨在探究瘢痕疙瘩成纤维细胞（KFbs）和相邻正常成纤维细胞（NFbs）中的自噬水平。此外，还研究了多嘧啶序列结合蛋白（PTB）是否通过自噬调节KFbs的生物学功能。
通过透射电子显微镜观察正常皮肤和瘢痕疙瘩中成纤维细胞的形态。我们用PTB特异性小干扰RNA（siRNA）沉默PTB，以确定PTB是否调节KFb增殖。进行吖啶橙和溶酶体追踪红染色以标记酸性区室。有趣的是，当用渥曼青霉素抑制自噬时，PTB敲低介导的KFb迁移和增殖的降低被消除，而I型和III型胶原蛋白水平未改变；这些结果表明PTB通过自噬调节KFbs的迁移和增殖，而胶原蛋白合成独立于PTB调节发生。
许多与KFbs存活和功能相关的活动受PTB控制。透射电子显微镜显示KFbs中的自噬体和自溶酶体比NFbs中的更多。吖啶橙和溶酶体追踪染色显示，PTB敲低后KFbs中自噬体数量显著增加，表明PTB诱导KFbs中的自噬。
我们的研究首次表明，PTB通过自噬调节KFbs的迁移和增殖，并且PTB以自噬非依赖的方式调节KFbs中的胶原蛋白合成。
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