Decorin attenuates hypertrophic scar fibrosis via TGFβ/Smad signalling

• Published in: Experimental dermatology 2024-07, Vol.33 (7), p.e15133-n/a
• Main Authors: Cui, Jiangtao, Zhang, Shiyi, Acharya, Kiran, Xu, Yan, Guo, Heng, Li, Tong, Fu, Donghe, Yang, Zizhen, Hou, Lingnan, Xing, Xiaotao, Hu, Xiaoyi
• Format: Article
• Language: English
• Subjects: Cell Movement; Cell Proliferation; Cells, Cultured; Cicatrix, Hypertrophic - metabolism; Cicatrix, Hypertrophic - pathology; Collagen; Collagen Type III - metabolism; Decorin; Decorin - metabolism; Extracellular matrix; fibroblasts; Fibroblasts - metabolism; Fibrosis; Humans; hypertrophic scar; Molecular modelling; Phosphorylation; proliferation; Scars; Signal Transduction; Smad protein; Smad3 protein; Smad3 Protein - metabolism; TGF‐β1/Smad3; Transforming Growth Factor beta1 - metabolism
• ISSN: 0906-6705; 1600-0625; 1600-0625
• DOI: 10.1111/exd.15133

The management of hypertrophic scars (HSs), characterized by excessive collagen production, involves various nonsurgical and surgical interventions. However, the absence of a well‐defined molecular mechanism governing hypertrophic scarring has led to less‐than‐ideal results in clinical antifibrotic treatments. Therefore, our study focused on the role of decorin (DCN) and its regulatory role in the TGF‐β/Smad signalling pathway in the development of HSs. In our research, we observed a decrease in DCN expression within hypertrophic scar tissue and its derived cells (HSFc) compared to that in normal tissue. Then, the inhibitory effect of DCN on collagen synthesis was confirmed in Fc and HSFc via the detection of fibrosis markers such as COL‐1 and COL‐3 after the overexpression and knockdown of DCN. Moreover, functional assessments revealed that DCN suppresses the proliferation, migration and invasion of HSFc. We discovered that DCN significantly inhibits the TGF‐β1/Smad3 pathway by suppressing TGF‐β1 expression, as well as the formation and phosphorylation of Smad3. This finding suggested that DCN regulates the synthesis of collagen‐based extracellular matrix and fibrosis through the TGF‐β1/Smad3 pathway. DCN knockdown siRNA and DCN‐overexpressing lentiviruses.Our research revealed that DCN not only reduces collagen accumulation within HSs but also hinders the proliferation, invasion and migration of HSFc. Moreover, DCN reduced fibrosis by inhibiting the TGF‐β1/Smad3 signalling pathway.