title: Phospholipase Cε deficiency delays the early stage of cutaneous wound healing and attenuates scar formation in mice.
abstract: This study aimed to investigate the role of phospholipase Cε (PLCε) in the skin wound healing process. PLCε, an effect factor of Ras/Rap small G protein, plays a crucial role in skin inflammation by regulating inflammatory cytokines. Inflammatory responses are closely associated with wound healing. Full-thickness skin wounds were made in the PLCε knockout (KO) and wild-type (WT) mice, and the healing process was analyzed. The macroscopic wound closure rate declined in the PLCε KO mice on days 3, 4, and 5 after wounding, following the decreased expression of interleukin (IL)-6, chemokine (C-X-C motif) ligand (Cxcl)-1, Cxcl-2, and chemokine (C-C motif) ligand (Ccl) 20. The proliferation rate of epidermal keratinocytes was not affected by PLCε, but silencing of PLCε resulted in the delayed migration of keratinocytes. Moreover, the scars were found to be much smaller in the PLCε KO mice than in the WT mice. The mRNA expression of Ccl20, collagen (Col) 6a1, and Col17a1 decreased in the PLCε KO mice. These results were in agreement with a previous hypothesis that PLCε might delay the early stage of cutaneous wound healing by inhibiting the migration of keratinocytes, and decrease the expression of Col6a1, Col17a1, and Ccl20 by inhibiting the inflammatory response to reduce scar formation. This study shed light on a novel role of PLCε in wound healing and provided new therapeutic approaches to target PLCε for diminishing scar formation after injury.
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Mu
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Pan
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Yunjuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Ning
authors.affiliation: Infection Section 15, The 302 Hospital of Chinese People's Liberation Army, Beijing, 100039, China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China.
authors.forename: Jiling
authors.initials: J
authors.lastname: Ren
authors.affiliation: Dermatology Services, University of California San Francisco, San Francisco, CA, 94121, USA.
authors.forename: Maoqiang
authors.initials: M
authors.lastname: Man
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China. Electronic address: liupeimei63@126.com.
authors.forename: Peimei
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070, China. Electronic address: lizhihu@tmu.edu.cn.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Hu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000235:genetics / Q000517:prevention & control*; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D020868:Gene Silencing; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015603:Keratinocytes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054801:Phosphoinositide Phospholipase C / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D034741:RNA, Small Interfering; D003094:Collagen; D054801:Phosphoinositide Phospholipase C; C423320:phospholipase C epsilon
keywords: Phospholipase Cε; Scar formation; Wound healing