PMID- 31746423 OWN - NLM STAT- MEDLINE DCOM- 20200603 LR - 20211008 IS - 1791-3004 (Electronic) IS - 1791-2997 (Print) IS - 1791-2997 (Linking) VI - 21 IP - 1 DP - 2020 Jan TI - Endoplasmic reticulum stress regulates epithelial‑mesenchymal transition in human lens epithelial cells. PG - 173-180 LID - 10.3892/mmr.2019.10814 [doi] AB - Epithelial‑to‑mesenchymal transition (EMT) of human lens epithelial cells (HLECs) serve an important role in cataract formation. The endoplasmic reticulum stress response (ER stress) has been demonstrated to regulate EMT in a number of tissues. The aim of the present study was to demonstrate the role of ER stress on EMT in HLECs. HLECs were treated with tunicamycin (TM) or thapsigargin (TG) to disturb ER homeostasis, and 4‑phenylbutyric acid (PBA) or sodium tauroursodeoxycholate (TUDCA) to restore ER homeostasis. Cell morphology was evaluated after 24 h. The long axis and aspect ratio of the cells were analyzed using ImageJ software. The results demonstrated that HLECs adopted an elongated morphology following treatment with TG, and the cellular aspect ratio increased. However, this morphological change was not observed following combination treatment with TG and PBA. Western blot analysis and immunofluorescence staining were used to measure the protein expression levels. A wound‑healing assay was performed to evaluate cell migration. Treatment with TM or TG increased the expression of the ER stress markers glucose‑regulated protein 78, phosphorylated eukaryotic initiation factor 2alpha, activating transcription factor (ATF)6, ATF4 and inositol‑requiring protein 1alpha and the EMT markers fibronectin, vimentin, alpha‑smooth muscle actin and neural cadherin. Furthermore, treatment with TM or TG decreased the expression of the epithelial cell marker epithelial cadherin and enhanced cell migration, which effects were inhibited following treatment with PBA or TUDCA. These results indicates that enhanced ER stress induced EMT and subsequently increased cell migration in HLECs in vitro. FAU - Zhou, Sheng AU - Zhou S AD - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China. FAU - Yang, Jing AU - Yang J AD - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China. FAU - Wang, Mingwei AU - Wang M AD - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China. FAU - Zheng, Danying AU - Zheng D AD - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China. FAU - Liu, Yizhi AU - Liu Y AD - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat‑sen University, Guangzhou, Guangdong 510060, P.R. China. LA - eng PT - Journal Article DEP - 20191112 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Eye Proteins) RN - 0 (Phenylbutyrates) RN - 11089-65-9 (Tunicamycin) RN - 516-35-8 (Taurochenodeoxycholic Acid) RN - 60EUX8MN5X (ursodoxicoltaurine) RN - 67526-95-8 (Thapsigargin) RN - 7WY7YBI87E (4-phenylbutyric acid) SB - IM MH - Cataract/metabolism/pathology MH - Cell Line MH - *Endoplasmic Reticulum Stress MH - Epithelial Cells/*metabolism/pathology MH - *Epithelial-Mesenchymal Transition MH - Eye Proteins/metabolism MH - Humans MH - Lens, Crystalline/*metabolism/pathology MH - Phenylbutyrates/pharmacology MH - Taurochenodeoxycholic Acid/pharmacology MH - Thapsigargin/pharmacology MH - Tunicamycin/pharmacology PMC - PMC6896292 OTO - NOTNLM OT - human lens epithelial cells OT - endoplasmic reticulum stress response OT - epithelial-to-mesenchymal transition OT - unfolded protein response EDAT- 2019/11/21 06:00 MHDA- 2020/06/04 06:00 PMCR- 2019/11/12 CRDT- 2019/11/21 06:00 PHST- 2019/05/08 00:00 [received] PHST- 2019/10/24 00:00 [accepted] PHST- 2019/11/21 06:00 [pubmed] PHST- 2020/06/04 06:00 [medline] PHST- 2019/11/21 06:00 [entrez] PHST- 2019/11/12 00:00 [pmc-release] AID - mmr-21-01-0173 [pii] AID - 10.3892/mmr.2019.10814 [doi] PST - ppublish SO - Mol Med Rep. 2020 Jan;21(1):173-180. doi: 10.3892/mmr.2019.10814. Epub 2019 Nov 12.