Reduction of PGRN increased fibrosis during skin wound healing in mice
Shan-shan Li1*, Mei-xiang Zhang1*, Yue Wang1, Wei Wang1, Chun-ming Zhao2, Xiao-ming Sun1, Guo-kai Dong1, Zhou-ru Li1, Wen-jiang Yin1, Bo Zhu3 and Hong-xing Cai1
1Department of Forensic Medicine, 2Department of Human Anatomy, Xuzhou Medical University, Xuzhou, Jiangsu, P.R. China and 3Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, Massachusetts, USA
*These authors contributed equally to this work
Offprint requests to: Professor Hongxing Cai, Deparment of Forensic Medicine, Xuzhou Medical University, 84 Western Huaihai Road, Xuzhou, Jiangsu 221000, P.R. China. e-mail: xzykdxchx@163.com
Summary. Progranulin (PGRN) is a multi-functional growth factor known to be involved in regulating of development, cell cycle progression, cell motility, tumorigenesis and angiogenesis. Research has revealed that PGRN is a crucial mediator of skin wound healing. Nonetheless, the role of PGRN in the fibrosis process of cutaneous wound healing has not been identified. In the present study, mice with excisional wounds were treated with si-m-PGRN or physiological saline. We observed the expression of PGRN in intact and post-injury skin by immunohistochemistry. Tissue sections of skin around the wound were performed by hematoxylin and eosin and masson's trichrome staining. After PGRN knockdown by siRNA, the expression of PGRN, collagen I (Col I), small mothers against decapentaplegic homolog 3 (Smad3), phosphorylated Smad3 (P-Smad3), transforming growth factor (TGF)-β1 and TGF-β receptor I (TβRI) were detected by real-time reverse transcription polymerase chain reaction (RT-qPCR) or Western blot. PGRN mRNA and protein expressions were increased after insult and remained above that of intact skin through day 20. Down-regulation of PGRN augmented fibrosis area, skin thickness and the expression of Col I. In addition, reduction of PGRN considerably increased the expression of TGF-β1, TβRI, Smad3 and P-Smad3. These results indicate that PGRN knockdown enhances the fibrosis degree, probably via the TGF-β/Smad signaling pathway. Histol Histopathol 34, 765-774 (2019)
Key words: Cutaneous wound healing, Fibrosis, PGRN, TGF-β/Smad
DOI: 10.14670/HH-18-076