Gas6 Prevents Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells via Production of PGE(2), PGD(2) and Their Receptors
- 주제(키워드) Gas6 , prostaglandins , epithelial-mesenchymal transition , alveolar epithelial cells
- 주제(기타) Cell Biology
- 설명문(일반) [Jung, Jihye; Lee, Ye-Ji; Choi, Youn-Hee; Kang, Jihee L.] Ewha Womans Univ, Sch Med, Dept Physiol, Seoul 07804, South Korea; [Jung, Jihye; Lee, Ye-Ji; Choi, Youn-Hee; Park, Eun-Mi; Kim, Hee-Sun; Kang, Jihee L.] Ewha Womans Univ, Sch Med, Tissue Injury Def Res Ctr, Seoul 07804, South Korea; [Park, Eun-Mi] Ewha Womans Univ, Sch Med, Dept Pharmacol, Seoul 07804, South Korea; [Kim, Hee-Sun] Ewha Womans Univ, Sch Med, Dept Mol Med, Seoul 07804, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, Green Submitted, gold
- 발행기관 MDPI
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000172011
- 본문언어 영어
- Published As https://dx.doi.org/10.3390/cells8070643
- PubMed https://pubmed.ncbi.nlm.nih.gov/31247991
초록/요약
The epithelial-mesenchymal transition (EMT) is important in organ fibrosis. We hypothesized that growth arrest -specific protein 6 (Gas6) and its underlying mechanisms play roles in the prevention of EMT in alveolar epithelial cells (ECs). In this study, to determine whether Gas6 prevents TGF-beta 1-induced EMT in LA-4 and primary alveolar type II ECs, real-time PCR and immunoblotting in cell lysates and ELISA in culture supernatants were performed. Migration and invasion assays were performed using Transwell chambers. Pretreatment of ECs with Gas6 inhibited TGF-beta 1-induced EMT based on cell morphology, changes in EMT marker expression, and induction of EMT-activating transcription factors. Gas6 enhanced the levels of cyclooxygenase-2 (COX-2)-derived prostaglandin E-2 (PGE(2)) and PGD(2) as well as of their receptors. COX -2 inhibitors and antagonists of PGE(2) and PGD2 receptors reversed the inhibition of TGF-beta 1-induced EMT, migration, and invasion by Gas6. Moreover, knockdown of Axl or Mer reversed the enhancement of PGE(2) and PGD(2) and suppression of EMT, migration and invasion by Gas6. Our data suggest Gas6-Axl or -Mer signalling events may reprogram ECs to resist EMT via the production of PGE(2), PGD(2), and their receptors.
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