Basic research

Role of autosis of fibroblasts in hypertrophic scar regression

  • Jian ZHANG ,
  • Fei SONG ,
  • Xiqiao WANG
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  • Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of Medical, Shanghai 200025, China
WANG Xiqiao, E-mail: wxqiao2002@hotmail.com.

Received date: 2021-09-27

  Online published: 2022-01-28

Supported by

National Natural Science Foundation of China(30872686)

Abstract

Objective

·To investigate whether autosis occurred in fibroblasts during hypertrophic scar regression.

Methods

·The scar tissues of 16 burn patients were collected from June 2018 to June 2019 in the Burn Department of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. They were divided into two groups: hyperplasia group (control group, 8 cases) and regression group (experimental group, 8 cases). Autophagy was observed by transmission electron microscopy. Fibroblasts of the two groups were cultured in vitro to establish a hypoxia model. The fibroblasts were collected at 12, 24 and 48 h respectively, and autophagy was observed by transmission electron microscopy. Live/dead cells were detected by using Calcein /PI fluorescent dye kit. The autophagy and apoptosis were observed by immunofluorescence. The numbers of apoptosis and autophagic death were detected by flow cytometry. Then the expression of hypoxia inducible factor1 (HIF-1), beclin-1, microtuble-associated protein light chain 3 (LC3), caspase-3 and caspase-9 were assayed at the protein level. Student's t test was used for quantitative data between the two groups, and One-way ANOVA test was used for quantitative data among multiple groups.

Results

·The electron microscopy showed that autophagosome existed in hyperplasia scar, and autosis occured in the regressive scar. In vitro study by electron microscopy was consistent with in vivo tissue observation. The dead cells had a marked increase at 24 hours, and further increased at 48 hours. Among them, the cell death type was mainly autosis, and a small amount of apoptosis. High expression of LC3 was responsible for this.

Conclusion

·In addition to apoptosis, autosis may be the major cell death during hypertrophic scar regression, and LC3 plays an important role.

Cite this article

Jian ZHANG , Fei SONG , Xiqiao WANG . Role of autosis of fibroblasts in hypertrophic scar regression[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(1) : 44 -50 . DOI: 10.3969/j.issn.1674-8115.2022.01.007

References

1 FENG Y, WU J J, SUN Z L, et al. Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation[J]. EBioMedicine, 2020, 54: 102715.
2 ZHENG J, SONG F, LU S L, et al. Dynamic hypoxia in scar tissue during human hypertrophic scar progression[J]. Dermatol Surg, 2014, 40(5): 511-518.
3 QURESHI B K, KUHN D, VIRY E, et al. Hypoxia-induced autophagy drives colorectal cancer initiation and progression by activating the PRKC/PKC-EZR (ezrin) pathway[J]. Autophagy, 2020, 16(8): 1436-1452.
4 MAIURI M C, ZALCKVAR E, KIMCHI A, et al. Self-eating and self-killing: crosstalk between autophagy and apoptosis[J]. Nat Rev Mol Cell Biol, 2007, 8(9): 741-752.
5 DONG Y, CHEN H W, GAO J L, et al. Molecular machinery and interplay of apoptosis and autophagy in coronary heart disease[J]. J Mol Cell Cardiol, 2019, 136: 27-41.
6 LEVINE B, MIZUSHIMA N, VIRGIN H W. Autophagy in immunity and inflammation[J]. Nature, 2011, 469(7330): 323-335.
7 LIU Y, LEVINE B. Autosis and autophagic cell death: the dark side of autophagy[J]. Cell Death Differ, 2015, 22(3): 367-376.
8 LIU Y, SHOJI-KAWATA S, SUMPTER R M, et al. Autosis is a Na+, K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia[J]. Proc Natl Acad Sci U S A, 2013, 110(51): 20364-20371.
9 ChUN Q, ZHIYONG W, FEI S, et al. Dynamic biological changes in fibroblasts during hypertrophic scar formation and regression[J]. Int Wound J, 2016, 13(2): 257-262.
10 CAO C, WANG W P, LU L L, et al. Inactivation of beclin-1-dependent autophagy promotes ursolic acid-induced apoptosis in hypertrophic scar fibroblasts[J]. Exp Dermatol, 2018, 27(1): 58-63.
11 ZHANG Y N, LIU D W, HU H J, et al. HIF-1α/BNIP3 signaling pathway-induced-autophagy plays protective role during myocardial ischemia-reperfusion injury[J]. Biomed Pharmacother, 2019, 120: 109464.
12 LU N, LI X X, Tan R L, et al. HIF-1α/beclin1-mediated autophagy is involved in neuroprotection induced by hypoxic preconditioning[J]. J Mol Neurosci, 2018, 66(2): 238-250.
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