Accelerated Wound Healing in Megakaryocyte/Platelet-Specific Fli1 Knockout Mice Due to the up-Regulated Expression of Interferon-γ

Megumi Hirabayashi¹, Yoshihide Asano², Takashi Yamashita¹, Ryosuke Saigusa¹, Shunsuke Miura³, Kouki Nakamura¹, Takuya Miyagawa¹, Takashi Taniguchi¹, Ayumi Yoshizaki¹ and Shinichi Sato⁴, ¹Dermatology, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, ²Applied Chemistry, University of Tokyo, Graduate School of Medicine, Tokyo, Japan, ³University of Tokyo, Graduate School of Medicine, Tokyo, Japan, ⁴Department of Dermatology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Angiogenesis, interferons, platelets, systemic sclerosis and wounds

Session Information

Date: Monday, November 6, 2017

Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's – Pathogenesis, Animal Models and Genetics Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Fli1 deficiency, a potential predisposing factor of systemic sclerosis (SSc), induces SSc-like phenotypes in dermal fibroblasts, endothelial cells, keratinocytes, and macrophages. However, it is still unclear how Fli1 deficiency affects the phenotype of platelets. Hence we aim to investigate the biological effect of Fli1-deficient platelets in vivo by utilizing megakaryocyte/platelet-specific Fli1 (Fli1 MPcKO) knockout mice (Fli1^flox/flox;Pf4-Cre).

Methods: Wound was generated by 8-mm punch device on the back skin of mice. Vascular structure was visualized by FITC-dextran injection. mRNA expression of target genes and collagen contents were assessed by quantitative reverse transcription PCR and hydroxyproline assay, respectively.

Results: Since Fli1 MPcKO mice macroscopically appeared normal, wound healing experiments were applied. Wound closure was accelerated in Fli1 MPcKO mice at Day 2 compared with control littermates, although there was no significant difference in the overall duration of wound closure between these two strains. When the expression profile of tissue remodeling-related factors was evaluated, interferon-g expression was significantly decreased in Fli1 MPcKO mice on Day 2. In the epithelized skin, collagen contents and the number of newly formed vasculature were much greater in Fli1 MPcKO mice than in control littermates. In addition, the number of a-smooth muscle actin-positive fusiform cells was increased in Fli1 MPcKO mice. Importantly, a mild skin injury, such as subcutaneous injection of PBS, induced extensive tissue fibrosis in Fli1 MPcKO mice.

Conclusion: Megakaryocyte/platelet-specific Fli1 deficiency promotes wound healing through the induction of myofibroblast differentiation and angiogenesis at least partially due to the downregulation of interferon-g. The activation of platelets with altered phenotype may contribute to the development of pathological skin fibrosis, including SSc.

Disclosure: M. Hirabayashi, None; Y. Asano, None; T. Yamashita, None; R. Saigusa, None; S. Miura, None; K. Nakamura, None; T. Miyagawa, None; T. Taniguchi, None; A. Yoshizaki, None; S. Sato, None.

To cite this abstract in AMA style:

Hirabayashi M, Asano Y, Yamashita T, Saigusa R, Miura S, Nakamura K, Miyagawa T, Taniguchi T, Yoshizaki A, Sato S. Accelerated Wound Healing in Megakaryocyte/Platelet-Specific Fli1 Knockout Mice Due to the up-Regulated Expression of Interferon-γ [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/accelerated-wound-healing-in-megakaryocyteplatelet-specific-fli1-knockout-mice-due-to-the-up-regulated-expression-of-interferon-%ce%b3/. Accessed .

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