2. Academic Validation
  3. Melatonin attenuates epidermal growth factor-induced cathepsin S expression in ARPE-19 cells: Implications for proliferative vitreoretinopathy

Melatonin attenuates epidermal growth factor-induced cathepsin S expression in ARPE-19 cells: Implications for proliferative vitreoretinopathy

  • J Pineal Res. 2020 Jan;68(1):e12615. doi: 10.1111/jpi.12615.
Shun-Fa Yang 1 2,  Yong-Syuan Chen 3,  Hsiang-Wen Chien 1 4 5,  Kai Wang 1 4 5,  Chia-Liang Lin 3,  Hui-Ling Chiou 6,  Chia-Yi Lee 7,  Pei-Ni Chen 3,  Yi-Hsien Hsieh 3 8 9
Affiliations

Affiliations

  • 1 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • 2 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
  • 3 Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan.
  • 4 Departments of Ophthalmology, Sijhih Cathay General Hospital, New Taipei City, Taiwan.
  • 5 Department of Ophthalmology, Cathay General Hospital, Taipei, Taiwan.
  • 6 Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
  • 7 Department of Ophthalmology, Show Chwan Memorial Hospital, Changhua, Taiwan.
  • 8 Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
  • 9 Clinical laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
PMID: 31605630 DOI: 10.1111/jpi.12615
Abstract

Abnormal proliferation and motility of retinal pigment epithelial cells leads to proliferative vitreoretinopathy (PVR). Melatonin is a known effective antitumour and anti-invasive agent, but whether it affects the formation and underlying mechanisms of PVR remains unclear. In this study, the results of the MTT assay, colony formation and propidium iodide (PI) staining with flow cytometry revealed that melatonin dose dependently inhibited epidermal growth factor (EGF)-induced proliferation of human ARPE-19 cells. Furthermore, melatonin reduced EGF-induced motility by suppressing Cathepsin S (CTSS) expression. Pretreatment with ZFL (a CTSS inhibitor) or overexpression of CTSS (pCMV-CTSS) significantly inhibited EGF-induced cell motility when combined with melatonin. Epidermal growth factor induced the phosphorylation of Akt(S473)/mTOR (S2448) and transcription factor (c-Jun/Sp1) signaling pathways. Pretreatment of LY294002 (a PI3K Inhibitor) or rapamycin (an mTOR Inhibitor) markedly reduced EGF-induced motility and p-AKT/p-mTOR/c-Jun/Sp1 expression when combined with melatonin. Taken together, these data indicate that melatonin inhibited EGF-induced proliferation and motility of human ARPE-19 cells by activating the Akt/mTOR pathway, which is dependent on CTSS modulation of c-Jun/Sp1 signalling. Melatonin may be a promising therapeutic drug against PVR.

Keywords

AKT; Sp1; c-Jun; cathepsin S; epidermal growth factor; mTOR; melatonin; motility; proliferation; retinal pigment epithelial cells.

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