Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi 710032, China.
State Key Laboratory of Military Stomatology, National Clinical Research Centre for Oral Diseases, Shaanxi International Joint Research Centre for Oral Diseases, Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, 127 Changle West Road, Xi'an, Shaanxi 710032, China.
Int J Biol Sci. 2022 May 9;18(8):3324-3336. doi: 10.7150/ijbs.71167. eCollection 2022.
Hypertrophic scars (HS) often occur after burns, surgery and extensive trauma. Krüppel-like factor 4 (KLF4) is a member of the Krüppel-like factor family, a group of conserved zinc finger transcription factors that regulate diverse cellular processes. KLF4 can participate in the regulation of fibrotic diseases in many organs, such as the lung, liver, and heart. However, the antifibrotic effect of KLF4 in skin HS remains elusive. This study observed the inhibition of KLF4 on fibrosis and . Our results revealed that KLF4 expression was decreased in HS tissue and fibroblasts. The results of KLF4 transfection confirmed its ability to alleviate the transdifferentiation of fibroblasts into myofibroblasts both and , thereby inhibiting the development of fibrosis. In addition, ChIP assays showed that BMP4 was the target gene of KLF4 for inhibiting skin fibrosis. Collectively, this evidence indicates that KLF4 is associated with BMP4 and could play an important regulatory role in HS formation by downregulating myofibroblast transdifferentiation. Our study provides a new target for the prevention and treatment of hypertrophic scars.
增生性瘢痕（HS）常发生于烧伤、手术和广泛创伤后。Krüppel 样因子 4（KLF4）是 Krüppel 样因子家族的成员，该家族是一组保守的锌指转录因子，可调节多种细胞过程。KLF4 可参与肺、肝和心脏等多个器官的纤维化疾病的调节。然而，KLF4 在皮肤 HS 中的抗纤维化作用仍不清楚。本研究观察了 KLF4 对纤维化的抑制作用。我们的结果表明，HS 组织和成纤维细胞中的 KLF4 表达减少。KLF4 转染的结果证实了它能够减轻成纤维细胞向肌成纤维细胞的转分化，从而抑制纤维化的发展。此外，ChIP 实验表明，BMP4 是 KLF4 抑制皮肤纤维化的靶基因。综上所述，这些证据表明，KLF4 与 BMP4 相关，通过下调肌成纤维细胞的转分化，在 HS 形成中发挥重要的调节作用。本研究为增生性瘢痕的防治提供了新的靶点。
