Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion

Jing Du; Wei Liu; Yajuan Song; Yu Zhang; Chen Dong; Shaoheng Xiong; Zhaosong Huang; Tong Wang; Jianke Ding; Qiang He; Zhou Yu; Xianjie Ma

doi:10.1093/burnst/tkad057

您当前的位置：

首页 >

文章列表页 >

Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion

更新时间：2024-04-19

- Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion
- Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion
- Burns & Trauma 2024年12卷第1期
- 作者机构：
  
  1. Department of Plastic Surgery, Xijing Hospital, Fourth Military Medical University
  2. Key Laboratory of Aerospace Medicine of Ministry of Education
  3. Fourth Military Medical University
- 作者简介：
- 基金信息：
  
  This work was supported by grants from the National Natural Science Foundation of China (82172229, 81971851, and 82102347), the Natural Science Basic Research Plan in Shaanxi Province of China (2022JM-600) and the Foundation of Xijing Hospital of Fourth Military Medical University Grants (XJZT21CM33).
- DOI：10.1093/burnst/tkad057
  中图分类号：
- 纸质出版日期：2024，
  
  网络出版日期：2024-2-7，
扫描看全文
Jing Du, Wei Liu, Yajuan Song, 等. Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion[J]. Burns & Trauma, 2024,12(1).

Jing Du, Wei Liu, Yajuan Song, Yu Zhang, Chen Dong, Shaoheng Xiong, Zhaosong Huang, Tong Wang, Jianke Ding, Qiang He, Zhou Yu, Xianjie Ma, Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion, Burns & Trauma, Volume 12, 2024, tkad057, https://doi.org/10.1093/burnst/tkad057
Jing Du, Wei Liu, Yajuan Song, 等. Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion[J]. Burns & Trauma, 2024,12(1). DOI： 10.1093/burnst/tkad057.

Jing Du, Wei Liu, Yajuan Song, Yu Zhang, Chen Dong, Shaoheng Xiong, Zhaosong Huang, Tong Wang, Jianke Ding, Qiang He, Zhou Yu, Xianjie Ma, Activating autophagy promotes skin regeneration induced by mechanical stretch during tissue expansion, Burns & Trauma, Volume 12, 2024, tkad057, https://doi.org/10.1093/burnst/tkad057 DOI：

摘要

Abstract

BackgroundTissue expansion

a technique in which skin regeneration is induced by mechanical stretch stimuli

is commonly used for tissue repair and reconstruction. In this study

we aimed to monitor the autophagy levels of expanded skin after the application of expansion stimuli and explore the effect of autophagy modulation on skin regeneration.MethodsA rat scalp expansion model was established to provide a stable expanded skin response to mechanical stretch. Autophagy levels at different time points (6

48 and 72 h after the last expansion) were detected via western blotting. The effect of autophagy regulation on skin regeneration during tissue expansion was evaluated via skin expansion efficiency assessment

western blotting

immunofluorescence staining

TUNEL staining and laser Doppler blood flow imaging.ResultsThe autophagic flux reached its highest level 48 h after tissue expansion. Activating autophagy by rapamycin increased the area of expanded skin as well as the thicknesses of epidermis and dermis. Furthermore

activating autophagy accelerated skin regeneration during tissue expansion by enhancing the proliferation of cells and the number of epidermal basal and hair follicle stem cells

reducing apoptosis

improving angiogenesis

and promoting collagen synthesis and growth factor secretion. Conversely

the regenerative effects were reversed when autophagy was blocked.ConclusionsAutophagy modulation may be a promising therapeutic strategy for improving the efficiency of tissue expansion and preventing the incidence of the complication of skin necrosis.

关键词

Keywords

AutophagyMechanical stretchSkin regenerationTissue expansion

references

1.Zöllner AM, Holland MA, Honda KS, Gosain AK, Kuhl E. Growth on demand: reviewing the mechanobiology of stretched skin. J Mech Behav Biomed Mater. 2013;28:495–509.

2.De Filippo RE, Atala A. Stretch and growth: the molecular and physiologic influences of tissue expansion. Plast Reconstr Surg. 2002;109:2450–62.

3.Azadgoli B, Fahradyan A, Wolfswinkel EM, Tsuha M, Magee W, Hammoudeh JA, et al. External port tissue expansion in the pediatric population: confirming its safety and efficacy. Plast Reconstr Surg. 2018;141:883e–90.

4.Patel PA, Elhadi HM, Kitzmiller WJ, Billmire DA, Yakuboff KP. Tissue expander complications in the pediatric burn patient: a 10-year follow-up. Ann Plast Surg. 2014;72:150–4.

5.Aragona M, Sifrim A, Malfait M, Song Y, Van Herck J, Dekoninck S, et al. Mechanisms of stretch-mediated skin expansion at single-cell resolution. Nature. 2020;584:268–73.

6.Razzak MA, Hossain MS, Radzi ZB, Yahya NAB, Czernuszka J, Rahman MT. Cellular and molecular responses to mechanical expansion of tissue. Front Physiol. 2016;7:540.

7.Doherty J, Baehrecke EH. Life, death and autophagy. Nat Cell Biol. 2018;20:1110–7.

8.Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J. Macroautophagy and selective mitophagy ameliorate chondrogenic differentiation potential in adipose stem cells of equine metabolic syndrome: new findings in the field of progenitor cells differentiation. Oxidative Med Cell Longev. 2016;2016:1–18.

9.Liang P, Jiang B, Li Y, Liu Z, Zhang P, Zhang M, et al. Autophagy promotes angiogenesis via AMPK/Akt/mTOR signaling during the recovery of heat-denatured endothelial cells. Cell Death Dis. 2018;9:1152.

10.Liu C, Zhou X, Lu J, Zhu L, Li M. Autophagy mediates 2-methoxyestradiol-inhibited scleroderma collagen synthesis and endothelial-to-mesenchymal transition induced by hypoxia. Rheumatology (Oxford). 2019;58:1966–75.

11.Chávez MN, Morales RA, López-Crisosto C, Roa JC, Allende ML, Lavandero S. Autophagy activation in zebrafish heart regeneration. Sci Rep. 2020;10:2191.

12.Mizushima N, Komatsu M. Autophagy: renovation of cells and tissues. Cell. 2011;147:728–41.

13.Varga M, Sass M, Papp D, Takács-Vellai K, Kobolak J, Dinnyés A, et al. Autophagy is required for zebrafish caudal fin regeneration. Cell Death Differ. 2014;21:547–56.

14.Saera-Vila A, Kish PE, KaW L, Grzegorski SJ, Klionsky DJ, Kahana A. Autophagy regulates cytoplasmic remodeling during cell reprogramming in a zebrafish model of muscle regeneration. Autophagy. 2016;12:1864–75.

15.Xie F, Xu S, Lu Y, Wong KF, Sun L, Hasan KMM, et al. Metformin accelerates zebrafish heart regeneration by inducing autophagy. NPJ Regen Med. 2021;6:62.

16.Chai M, Jiang M, Vergnes L, Fu X, de Barros SC, Doan NB, et al. Stimulation of hair growth by small molecules that activate autophagy. Cell Rep. 2019;27:3413–3421.e3.

17.Kim SW, Ehrman J, Ahn M-R, Kondo J, Lopez AAM, Oh YS, et al. Shear stress induces noncanonical autophagy in intestinal epithelial monolayers. Mol Biol Cell. 2017;28:3043–56.

18.Yurube T, Hirata H, Ito M, Terashima Y, Kakiuchi Y, Kuroda R, et al. Involvement of autophagy in rat tail static compression-induced intervertebral disc degeneration and notochordal cell disappearance. Int J Mol Sci. 2021;22:5648.

19.King JS, Veltman DM, Insall RH. The induction of autophagy by mechanical stress. Autophagy. 2011;7:1490–9.

20.Ma KG, Shao ZW, Yang SH, Wang J, Wang BC, Xiong LM, et al. Autophagy is activated in compression-induced cell degeneration and is mediated by reactive oxygen species in nucleus pulposus cells exposed to compression. Osteoarthr Cartil. 2013;21:2030–8.

21.Jiang N, He D, Ma Y, Su J, Wu X, Cui S, et al. Force-induced autophagy in periodontal ligament stem cells modulates M1 macrophage polarization via AKT signaling. Front Cell Dev Biol. 2021;9:666631.

22.Blawat K, Mayr A, Hardt M, Kirschneck C, Nokhbehsaim M, Behl C, et al. Regulation of autophagic signaling by mechanical loading and inflammation in human PDL fibroblasts. Int J Mol Sci. 2020;21:9446.

23.Liu S, Ding J, Zhang Y, Cheng X, Dong C, Song Y, et al. Establishment of a novel mouse model for soft tissue expansion. J Surg Res. 2020;253:238–44.

24.Yu Z, Liu S, Cui J, Song Y, Wang T, Song B, et al. Early histological and ultrastructural changes in expanded murine scalp. Ultrastruct Pathol. 2020;44:141–52.

25.Robke L, Laraia L, Carnero Corrales MA, Konstantinidis G, Muroi M, Richters A, et al. Phenotypic identification of a novel autophagy inhibitor chemotype targeting lipid kinase VPS34. Angew Chem Int Ed Engl. 2017;56:8153–7.

26.Liu W, Xiong S, Zhang Y, Du J, Dong C, Yu Z, et al. Transcriptome profiling reveals important transcription factors and biological processes in skin regeneration mediated by mechanical stretch. Front Genet. 2021;12:757350.

27.Kim YC, Guan K-L. mTOR: a pharmacologic target for autophagy regulation. J Clin Invest. 2015;125:25–32.

28.Pandey M, Belgamwar V, Gattani S, Surana S, Tekade A. Pluronic lecithin organogel as a topical drug delivery system. Drug Deliv. 2010;17:38–47.

29.Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, et al. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. 2021;17:1–382.

30.Dekoninck S, Blanpain C. Stem cell dynamics, migration and plasticity during wound healing. Nat Cell Biol. 2019;21:18–24.

31.Jung M, Jang I, Kim K, Moon KC. CK14 expression identifies a basal/squamous-like type of papillary non-muscle-invasive upper tract urothelial carcinoma. Front Oncol. 2020;10:623.

32.Amoh Y, Kanoh M, Niiyama S, Hamada Y, Kawahara K, Sato Y, et al. Human hair follicle pluripotent stem (hfPS) cells promote regeneration of peripheral-nerve injury: an advantageous alternative to ES and iPS cells. J Cell Biochem. 2009;107:1016–20.

33.Yang M, Li Q, Sheng L, Li H, Weng R, Zan T. Bone marrow-derived mesenchymal stem cells transplantation accelerates tissue expansion by promoting skin regeneration during expansion. Ann Surg. 2011;253:202–9.

34.Klionsky DJ, Petroni G, Amaravadi RK, Baehrecke EH, Ballabio A, Boya P, et al. Autophagy in major human diseases. EMBO J. 2021;40:e108863.

35.Ko S-H, Apple EC, Liu Z, Chen L. Age-dependent autophagy induction after injury promotes axon regeneration by limiting NOTCH. Autophagy. 2020;16:2052–68.

36.García-Prat L, Martínez-Vicente M, Perdiguero E, Ortet L, Rodríguez-Ubreva J, Rebollo E, et al. Autophagy maintains stemness by preventing senescence. Nature. 2016;529:37–42.

37.Xu F, Hua C, Tautenhahn H-M, Dirsch O, Dahmen U. The role of autophagy for the regeneration of the aging liver. Int J Mol Sci. 2020;21:3606.

38.Sotiropoulou PA, Blanpain C. Development and homeostasis of the skin epidermis. Cold Spring Harb Perspect Biol. 2012;4:a008383.

39.Madrid A, Cardile V, González C, Montenegro I, Villena J, Caggia S, et al. Psoralea glandulosa as a potential source of anticancer agents for melanoma treatment. Int J Mol Sci. 2015;16:7944–59.

40.Luo Z, Xu X, Sho T, Zhang J, Xu W, Yao J, et al. ROS-induced autophagy regulates porcine trophectoderm cell apoptosis, proliferation, and differentiation. Am J Physiol Cell Physiol. 2019;316:C198–209.

41.Maiuri MC, Zalckvar E, Kimchi A, Kroemer G. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 2007;8:741–52.

42.Ren H, Zhao F, Zhang Q, Huang X, Wang Z. Autophagy and skin wound healing. Burns Trauma. 2022;10:tkac003.

43.Wang E-j, Wu M-Y, Ren Z-y, Zheng Y, Ye RD, TAN CSH, et al. Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease. Burns Trauma. 2023;11:tkac004.

44.Ehrlich F, Fischer H, Langbein L, Praetzel-Wunder S, Ebner B, Figlak K, et al. Differential evolution of the epidermal keratin cytoskeleton in terrestrial and aquatic mammals. Mol Biol Evol. 2019;36:328–40.

45.Lyle S, Christofidou-Solomidou M, Liu Y, Elder DE, Albelda S, Cotsarelis G. The C8/144B monoclonal antibody recognizes cytokeratin 15 and defines the location of human hair follicle stem cells. J Cell Sci. 1998;111:3179–88.

46.Adam RC, Yang H, Ge Y, Lien W-H, Wang P, Zhao Y, et al. Temporal layering of Signaling effectors drives chromatin Remodeling during hair follicle stem cell lineage progression. Cell Stem Cell. 2018;22:398–413.e7.

47.Dong C, Zhu M, Huang L, Liu W, Liu H, Jiang K, et al. Risk factors for tissue expander infection in scar reconstruction: a retrospective cohort study of 2374 consecutive cases. Burns Trauma. 2020;9:tkaa037.

48.Huang X, Qu X, Li Q. Risk factors for complications of tissue expansion: a 20-year systematic review and meta-analysis. Plast Reconstr Surg. 2011;128:787–97.

49.Huang X, Liang X, Zhou Y, Li H, Du H, Suo Y, et al. CDH1 is identified as a therapeutic target for skin regeneration after mechanical loading. Int J Biol Sci. 2021;17:353–67.

50.Carmeliet P. Angiogenesis in life, disease and medicine. Nature. 2005;438:932–6.

51.Zhang S, Liu Y, Zhang X, Zhu D, Qi X, Cao X, et al. Prostaglandin E hydrogel improves cutaneous wound healing via M2 macrophages polarization. Theranostics. 2018;8:5348–61.

52.Talwar HS, Griffiths CE, Fisher GJ, Hamilton TA, Voorhees JJ. Reduced type I and type III procollagens in photodamaged adult human skin. J Invest Dermatol. 1995;105:285–90.

53.Boudko SP, Engel J, Okuyama K, Mizuno K, Bächinger HP, Schumacher MA. Crystal structure of human type III collagen Gly991-Gly1032 cystine knot-containing peptide shows both 7/2 and 10/3 triple helical symmetries. J Biol Chem. 2008;283:32580–9.

54.Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008;16:585–601.

55.Lin S-Y, Li TY, Liu Q, Zhang C, Li X, Chen Y, et al. GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to autophagy. Science. 2012;336:477–81.

56.Natarajan A, Wagner B, Sibilia M. The EGF receptor is required for efficient liver regeneration. Proc Natl Acad Sci U S A. 2007;104:17081–6.

57.Cross MJ, Claesson-Welsh L. FGF and VEGF function in angiogenesis: signalling pathways, biological responses and therapeutic inhibition. Trends Pharmacol Sci. 2001;22:201–7.

58.Zhang X, Kang X, Jin L, Bai J, Liu W, Wang Z. Stimulation of wound healing using bioinspired hydrogels with basic fibroblast growth factor (bFGF). Int J Nanomedicine. 2018;13:3897–906.

59.Ihn H. Pathogenesis of fibrosis: role of TGF-beta and CTGF. Curr Opin Rheumatol. 2002;14:681–5.

60.Hosui A, Kimura A, Yamaji D, Zhu B-m, Na R, Hennighausen L. Loss of STAT5 causes liver fibrosis and cancer development through increased TGF-{beta} and STAT3 activation. J Exp Med. 2009;206:819–31.

查看原文

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy

S100 calcium-binding protein A9 promotes skin regeneration through toll-like receptor 4 during tissue expansion

Targeting macrophage autophagy for inflammation resolution and tissue repair in inflammatory bowel disease

Polymeric biomaterials-based tissue engineering for wound healing: a systemic review

Autophagy in the pathogenesis and therapeutic potential of post-traumatic osteoarthritis