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. 2021 Mar 3:15:973-981.
doi: 10.2147/DDDT.S280322. eCollection 2021.

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Xiaoyuan Wang  1 , Wuqi Song  2 , Fengmin Zhang  2 , Renping Huang  3
Affiliations

Dihydroartemisinin Inhibits TGF-β-Induced Fibrosis in Human Tenon Fibroblasts via Inducing Autophagy

Xiaoyuan Wang et al. Drug Des Devel Ther. .

Abstract

Background: The formation of hypertrophic scars (HS) can result in the failure of glaucoma surgery, and fibrosis is known to be closely associated with the progression of HS. Dihydroartemisinin (DHA) has been reported to inhibit the progression of fibrosis; however, whether DHA can alleviate the formation of HS remains unclear.

Methods: In the present study, in order to examine the effects of DHA on the progression of HS, human Tenon's capsule fibroblasts (HTFs) were isolated from patients who underwent glaucoma surgery. In addition, Western blot analysis, microtubule associated protein 1 light chain 3 α staining and reverse transcription-quantitative PCR were performed to detect protein and mRNA expression levels in the HTFs, respectively. Cell proliferation was detected by Ki67 staining. Flow cytometry was used to examine apoptosis and reactive oxygen species (ROS) levels in the HTFs.

Results: The results revealed that TGF-β promoted the proliferation and fibrosis of HTFs; however, DHA significantly reversed the effects of TGF-β by increasing cell autophagy. In addition, DHA notably induced the apoptosis of TGF-β-stimulated HTFs by increasing the ROS levels, while these increases were partially reversed by 3-methyladenine. Furthermore, DHA notably increased the expression of microRNA (miR)-145-5p in HTFs in a dose-dependent manner.

Conclusion: The present study demonstrated that DHA inhibits the TGF-β-induced fibrosis of HTFs by inducing autophagy. These findings may aid in the development of novel agents for the prevention of the formation of HS following glaucoma surgery.

Keywords: DHA; HS; HTFs; autophagy; fibrosis.

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Conflict of interest statement

The authors declared no competing interests in this work.

Figures

Figure 1
Figure 1
HTFs were successfully isolated.
Figure 2
Figure 2
DHA significantly reversed TGF-β-induced proliferation in HTFs.
Figure 3
Figure 3
DHA inhibited TGF-β-induced fibrosis in HTFs via inducing autophagy.
Figure 4
Figure 4
Autophagy inhibitor partially reversed DHA-induced oxidative stress in TGF-β-treated HTFs.
Figure 5
Figure 5
DHA-induced apoptosis in TGF-β-treated HTFs was partially reversed by 3-MA.
Figure 6
Figure 6
DHA notably upregulated the expression of miR-145-5p in HTFs.
See this image and copyright information in PMC

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