Phospholipase Cε deficiency delays the early stage of cutaneous wound healing and attenuates scar formation in mice

Journal Article · Sun Feb 26 04:00:00 EST 2017 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2017.01.054· OSTI ID:22696876

Zhu, Xiaolong; Sun, Yue; Mu, Xin; Guo, Pan; Gao, Fei; Zhang, Jing; Zhu, Yunjuan; Zhang, Xianzhi; Chen, Lingling ^[1]; Ning, Zhiwei ^[2]; Bai, Yunfeng ^[3]; Ren, Jiling ^[1]; Man, Maoqiang ^[4]; Liu, Peimei ^[1]; Hu, Lizhi ^[1]

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1. Department of Pathogen Biology and Immunology, Basic Medical College, Tianjin Medical University, Tianjin, 300070 (China)
2. Department of Endocrinology and Metabolism, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020 (China)
3. Infection Section 15, The 302 Hospital of Chinese People's Liberation Army, Beijing, 100039 (China)
4. Dermatology Services, University of California San Francisco, San Francisco, CA, 94121 (United States)

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. - Highlights: • Phospholipase Cε deficiency inhibits scar formation. • Phospholipase Cε involves inflammatory cytokine production during wound healing. • Phospholipase Cε deficiency reduces keratinocyte migration. • Phospholipase Cε deficiency decreases collagen production in vivo and in vitro.

• OSTI ID: 22696876
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 484; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
HEALING
INFLAMMATION
INHIBITION
KNOCK-OUT REACTIONS
LYMPHOKINES
MICE
MIGRATION
SKIN
VISIBLE RADIATION
WOUNDS