Alghamdi Mansour A, Al-Eitan Laith N, Stevenson Andrew, Chaudhari Nutan, Hortin Nicole, Wallace Hilary J, Danielsen Patricia L, Manzur Mitali, Wood Fiona M, Fear Mark W
Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia.
Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia.
Biomedicines. 2020 Jul 8;8(7):200. doi: 10.3390/biomedicines8070200.
Interactions between keratinocytes and fibroblasts in the skin layers are crucial in normal tissue development, wound healing, and scarring. This study has investigated the role of keloid keratinocytes in regulating collagen production by primary fibroblasts in vitro. Keloid cells were obtained from removed patients' tissue whereas normal skin cells were discarded tissue obtained from elective surgery procedures. Fibroblasts and keratinocytes were isolated, cultured, and a transwell co-culture system were used to investigate the effect of keratinocytes on collagen production using a 'scar-in-a-jar' model. Keloid fibroblasts produced significantly more collagen than normal skin fibroblasts in monoculture at the RNA, secreted protein, and stable fibrillar protein level. When keloid keratinocytes were added to normal skin fibroblasts, expression of collagen was significantly upregulated in most samples, but when added to keloid fibroblasts, collagen I production was significantly reduced. Interestingly, keloid keratinocytes appear to decrease collagen production by keloid fibroblasts. This suggests that signaling in both keratinocytes and fibroblasts is disrupted in keloid pathology.
皮肤各层中角质形成细胞与成纤维细胞之间的相互作用在正常组织发育、伤口愈合和瘢痕形成过程中至关重要。本研究调查了瘢痕疙瘩角质形成细胞在体外调节原代成纤维细胞胶原蛋白产生中的作用。瘢痕疙瘩细胞取自切除的患者组织,而正常皮肤细胞则取自择期手术中丢弃的组织。分离、培养成纤维细胞和角质形成细胞,并使用Transwell共培养系统,采用“罐中瘢痕”模型研究角质形成细胞对胶原蛋白产生的影响。在单培养中,瘢痕疙瘩成纤维细胞在RNA、分泌蛋白和稳定纤维状蛋白水平上产生的胶原蛋白明显多于正常皮肤成纤维细胞。当将瘢痕疙瘩角质形成细胞添加到正常皮肤成纤维细胞中时,大多数样本中胶原蛋白的表达显著上调,但当添加到瘢痕疙瘩成纤维细胞中时,I型胶原蛋白的产生显著减少。有趣的是,瘢痕疙瘩角质形成细胞似乎会减少瘢痕疙瘩成纤维细胞的胶原蛋白产生。这表明在瘢痕疙瘩病理过程中,角质形成细胞和成纤维细胞中的信号传导均受到破坏。