CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells

Xiaoqiang Liu; Jinrui Yang; Meng Kong; Min Jiang; Luojia Liu; Jinghong Zhang; Ying Chen; Xu Chen; Ze Zhang; Chao Wu; Xupin Jiang; Jie Liu; Jiaping Zhang

doi:10.1093/burnst/tkad012

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CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells

更新时间：2023-08-29

- CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells
- CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells
- Burns & Trauma 2023年11卷第1期
- 作者机构：
  
  1. Department of Plastic Surgery
  2. Third Military Medical University (Army Medical University)
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad012
  中图分类号：
- 纸质出版日期：2023，
  
  网络出版日期：2023-7-24，
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Xiaoqiang Liu, Jinrui Yang, Meng Kong, 等. CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells[J]. Burns & Trauma, 2023,11(1).

Xiaoqiang Liu, Jinrui Yang, Meng Kong, Min Jiang, Luojia Liu, Jinghong Zhang, Ying Chen, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jie Liu, Jiaping Zhang, CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells, Burns & Trauma, Volume 11, 2023, tkad012, https://doi.org/10.1093/burnst/tkad012
Xiaoqiang Liu, Jinrui Yang, Meng Kong, 等. CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells[J]. Burns & Trauma, 2023,11(1). DOI： 10.1093/burnst/tkad012.

Xiaoqiang Liu, Jinrui Yang, Meng Kong, Min Jiang, Luojia Liu, Jinghong Zhang, Ying Chen, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jie Liu, Jiaping Zhang, CD9 negatively regulates collective electrotaxis of the epidermal monolayer by controlling and coordinating the polarization of leader cells, Burns & Trauma, Volume 11, 2023, tkad012, https://doi.org/10.1093/burnst/tkad012 DOI：

摘要

Abstract

BackgroundEndogenous electric fields (EFs) play an essential role in guiding the coordinated collective migration of epidermal cells to the wound centre during wound healing. Although polarization of leadercells is essential for collective migration

the signal mechanisms responsible for the EF-induced polarization of leader cells under electrotactic collective migration remain unclear. This study aims to determine how the leader cells are polarized and coordinated during EF-guided collective migration of epidermal cell sheets.MethodsCollective migration of the human epidermal monolayer (human immortalized keratinocytes HaCaT) under EFs was observed via time-lapse microscopy. The involvement of tetraspanin-29 (CD9) in EF-induced fibrous actin (F-actin) polarization of leader cells as well as electrotactic migration of the epidermal monolayer was evaluated by genetic manipulation. Blocking

rescue and co-culture experiments were conducted to explore the downstream signalling of CD9.ResultsEFs guided the coordinated collective migration of the epithelial monolayer to the anode

with dynamic formation of pseudopodia in leader cells at the front edge of the monolayer along the direction of migration. F-actin polarization

as expected

played an essential role in pseudopod formation in leader cells under EFs. By confocal microscopy

we found that CD9 was colocalized with F-actin on the cell surface and was particularly downregulated in leader cells by EFs. Interestingly

genetic overexpression of CD9 abolished EF-induced F-actin polarization in leader cells as well as collective migration in the epidermal monolayer. Mechanistically

CD9 determined the polarization of F-actin in leader cells by downregulating a disintegrin and metalloprotease 17/heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor (ADAM17/HB-EGF/EGFR) signalling. The abolished polarization of leader cells due to CD9 overexpression could be restored in a co-culture monolayer where normal cells and CD9-overexpressing cells were mixed; however

this restoration was eliminated again by the addition of the HB-EGF-neutralizing antibody.ConclusionCD9 functions as a key regulator in the EF-guided collective migration of the epidermal monolayer by controlling and coordinating the polarization of leader cells through ADAM17/HB-EGF/EGFR signalling.

关键词

Keywords

CD9Electric fieldsCollective migrationWound healingF-actin polarizationleader cells

references

1.Shaw TJ, Martin P. Wound repair at a glance. J Cell Sci. 2009;122:3209–13.

2.Xiao T, Yan Z, Xiao S, Xia Y. Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization. Stem Cell Res Ther. 2020;11:232.

3.Kruse CR, Singh M, Targosinski S, Sinha I, Sorensen JA, Eriksson E, et al. The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: in vitro and in vivo study. Wound Repair Regen. 2017;25:260–9.

4.Sun YS. Electrical stimulation for wound-healing: simulation on the effect of electrode configurations. Biomed Res Int. 2017;2017:5289041.

5.Yang J, Liu X, Wang W, Chen Y, Liu J, Zhang Z, et al. Bioelectric fields coordinate wound contraction and re-epithelialization process to accelerate wound healing via promoting myofibroblast transformation. Bioelectrochemistry. 2022;148:108247.

6.Zhao M. Electrical fields in wound healing-an overriding signal that directs cell migration. Semin Cell Dev Biol. 2009;20:674–82.

7.Hart FX, Laird M, Riding A, Pullar CE. Keratinocyte galvanotaxis in combined DC and AC electric fields supports an electromechanical transduction sensing mechanism. Bioelectromagnetics. 2013;34:85–94.

8.Zhao M, McCaig CD, Agius-Fernandez A, Forrester JV, Araki-Sasaki K. Human corneal epithelial cells reorient and migrate cathodally in a small applied electric field. Curr Eye Res. 1997;16:973–84.

9.Li L, Hartley R, Reiss B, Sun Y, Pu J, Wu D, et al. E-cadherin plays an essential role in collective directional migration of large epithelial sheets. Cell Mol Life Sci. 2012;69:2779–89.

10.Lalli ML, Asthagiri AR. Collective migration exhibits greater sensitivity but slower dynamics of alignment to applied electric fields. Cell Mol Bioeng. 2015;8:247–57.

11.Debets VE, Janssen LMC, Storm C. Enhanced persistence and collective migration in cooperatively aligning cell clusters. Biophys J. 2021;120:1483–97.

12.Mayor R, Etienne-Manneville S. The front and rear of collective cell migration. Nat Rev Mol Cell Biol. 2016;17:97–109.

13.Qin L, Yang D, Yi W, Cao H, Xiao G. Roles of leader and follower cells in collective cell migration. Mol Biol Cell. 2021;32:1267–72.

14.Schaks M, Giannone G, Rottner K. Actin dynamics in cell migration. Essays Biochem. 2019;63:483–95.

15.Cook GA, Longhurst CM, Grgurevich S, Cholera S, Crossno JT, Jr, Jennings LK. Identification of CD9 extracellular domains important in regulation of CHO cell adhesion to fibronectin and fibronectin pericellular matrix assembly. Blood. 2002;100:4502–11.

16.Chen S, Sun Y, Jin Z, Jing X. Functional and biochemical studies of CD9 in fibrosarcoma cell line. Mol Cell Biochem. 2011;350:89–99.

17.Matthews AL, Noy PJ, Reyat JS, Tomlinson MG. Regulation of a disintegrin and metalloproteinase (ADAM) family sheddases ADAM10 and ADAM17: the emerging role of tetraspanins and rhomboids. Platelets. 2017;28:333–41.

18.Charrin S, Jouannet S, Boucheix C, Rubinstein E. Tetraspanins at a glance. J Cell Sci. 2014;127:3641–8.

19.Hemler ME. Tetraspanin proteins promote multiple cancer stages. Nat Rev Cancer. 2014;14:49–60.

20.Liu J, Zhu G, Jia N, Wang W, Wang Y, Yin M, et al. CD9 regulates keratinocyte migration by negatively modulating the sheddase activity of ADAM17. Int J Biol Sci. 2019;15:493–506.

21.Li Y, Ren Z, Wang Y, Dang YZ, Meng BX, Wang GD, et al. ADAM17 promotes cell migration and invasion through the integrin beta1 pathway in hepatocellular carcinoma. Exp Cell Res. 2018;370:373–82.

22.Soto-Gamez A, Chen D, Nabuurs AGE, Quax WJ, Demaria M, Boersma YL. A bispecific inhibitor of the EGFR/ADAM17 axis decreases cell proliferation and migration of EGFR-dependent cancer cells. Cancers (Basel). 2020;12:411.

23.Jia N, Liu J, Zhu G, Liang Y, Wang Y, Wang W, et al. Polarization of ADAM17-driven EGFR signalling in electric field-guided collective migration of epidermal sheets. J Cell Mol Med. 2020;24:14073–85.

24.Combedazou A, Gayral S, Colombie N, Fougerat A, Laffargue M, Ramel D. Small GTPases orchestrate cell-cell communication during collective cell movement. Small GTPases. 2020;11:103–12.

25.Rappel WJ. Cell-cell communication during collective migration. Proc Natl Acad Sci U S A. 2016;113:1471–3.

26.Han Y, You X, Xing W, Zhang Z, Zou W. Paracrine and endocrine actions of bone-the functions of secretory proteins from osteoblasts, osteocytes, and osteoclasts. Bone Res. 2018;6:16.

27.Huising MO. Paracrine regulation of insulin secretion. Diabetologia. 2020;63:2057–63.

28.Kim S, Subramanian V, Abdel-Latif A, Lee S. Role of heparin-binding epidermal growth factor-like growth factor in oxidative stress-associated metabolic diseases. Metab Syndr Relat Disord. 2020;18:186–96.

29.Lian C, Ruan L, Shang D, Wu Y, Lu Y, Lu P, et al. Heparin-binding epidermal growth factor-like growth factor as a potent target for breast cancer therapy. Cancer Biother Radiopharm. 2016;31:85–90.

30.Liu J, Guo X, Ren X, Tian H, Liang Y, Luo Z, et al. A novel FPCL model producing directional contraction through induction of fibroblast alignment by biphasic pulse direct current electric field. Exp Cell Res. 2018;371:426–34.

31.Zhang J, Calafiore M, Zeng Q, Zhang X, Huang Y, Li RA, et al. Electrically guiding migration of human induced pluripotent stem cells. Stem Cell Rev Rep. 2011;7:987–96.

32.Poukkula M, Hakala M, Pentinmikko N, Sweeney MO, Jansen S, Mattila J, et al. GMF promotes leading-edge dynamics and collective cell migration in vivo. Curr Biol. 2014;24:2533–40.

33.Cai L, Xu D, Chen H, Wang L, Zhao Y. Designing bioactive micro−/nanomotors for engineered regeneration. Eng Regen. 2021;2:109–15.

34.Luo Z, Che J, Sun L, Yang L, Zu Y, Wang H, et al. Microfluidic electrospray photo-crosslinkable κ-carrageenan microparticles for wound healing. Eng Regen. 2021;2:257–62.

35.Yu Y, Wang Q, Wang C, Shang L. Living materials for regenerative medicine. Eng Regen. 2021;2:96–104.

36.Luo R, Dai J, Zhang J, Li Z. Accelerated skin wound healing by electrical stimulation. Adv Healthc Mater. 2021;10:e2100557.

37.Liang Y, Tian H, Liu J, Lv Y, Wang Y, Zhang J, et al. Application of stable continuous external electric field promotes wound healing in pig wound model. Bioelectrochemistry. 2020;135:107578.

38.Grada A, Otero-Vinas M, Prieto-Castrillo F, Obagi Z, Falanga V. Research techniques made simple: analysis of collective cell migration using the wound healing assay. J Invest Dermatol. 2017;137:e11–6.

39.Zhu K, Hum NR, Reid B, Sun Q, Loots GG, Zhao M. Electric fields at breast cancer and cancer cell collective galvanotaxis. Sci Rep. 2020;10:8712.

40.Gao J, Raghunathan VK, Reid B, Wei D, Diaz RC, Russell P, et al. Biomimetic stochastic topography and electric fields synergistically enhance directional migration of corneal epithelial cells in a MMP-3-dependent manner. Acta Biomater. 2015;12:102–12.

41.Rorth P. Collective guidance of collective cell migration. Trends Cell Biol. 2007;17:575–9.

42.Khalil AA, Friedl P. Determinants of leader cells in collective cell migration. Integr Biol (Camb). 2010;2:568–74.

43.Haeger A, Wolf K, Zegers MM, Friedl P. Collective cell migration: guidance principles and hierarchies. Trends Cell Biol. 2015;25:556–66.

44.Freedman SL, Suarez C, Winkelman JD, Kovar DR, Voth GA, Dinner AR, et al. Mechanical and kinetic factors drive sorting of F-actin cross-linkers on bundles. Proc Natl Acad Sci U S A. 2019;116:16192–7.

45.Seetharaman S, Etienne-Manneville S. Cytoskeletal crosstalk in cell migration. Trends Cell Biol. 2020;30:720–35.

46.Sackmann E. How actin/myosin crosstalks guide the adhesion, locomotion and polarization of cells. Biochim Biophys Acta. 2015;1853:3132–42.

47.Zhao M, Pu J, Forrester JV, McCaig CD. Membrane lipids, EGF receptors, and intracellular signals colocalize and are polarized in epithelial cells moving directionally in a physiological electric field. FASEB J. 2002;16:857–9.

48.Fang KS, Ionides E, Oster G, Nuccitelli R, Isseroff RR. Epidermal growth factor receptor relocalization and kinase activity are necessary for directional migration of keratinocytes in DC electric fields. J Cell Sci. 1999;112:1967–78.

49.Zhao M, Song B, Pu J, Wada T, Reid B, Tai G, et al. Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN. Nature. 2006;442:457–60.

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