- 作者: Nozomi Igarashi, Megumi Honjo, Reiko Yamagishi, Makoto Kurano, Yutaka Yatomi, Koji Igarashi, Toshikatsu Kaburaki and Makoto Aihara
- 作者服務機構: 1.Department of Ophthalmology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan 2.Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo, 113-8655, Japan 3.CREST, Japan Science and Technology Corporation (JST), Saitama, Japan 4.Department of Clinical Laboratory, The University of Tokyo Hospital, Tokyo, Japan 5.Bioscience Division, Reagent Development Department, AIA Research Group, TOSOH Corporation, Kanagawa, Japan 6.Department of Ophthalmology, Jichi Medical University Saitama Medical Center, Saitama, Japan
- 中文摘要:
- 英文摘要:
Background
Elevated transforming growth factor (TGF)-β2 in aqueous humor (AH) has been suggested to contribute to trabecular meshwork (TM) fibrosis and intraocular pressure (IOP) regulation in primary open-angle glaucoma (POAG), but TGF-β2 is downregulated in secondary open-angle glaucoma (SOAG). Because autotaxin (ATX) is upregulated in SOAG, we investigated the relationships and trans-signaling interactions of these mediators.
Methods
The level of ATX in AH was determined using a two-site immunoenzymetric assay, and TGF-β levels were measured using the Bio-Plex Pro TGF-β Assay. RNA scope was used to assess the expression of ATX and TGF-β2 in human’s eye specimen. And in vitro studies were performed using hTM cells to explore if trans-signaling of TGF-β2 regulates ATX expressions.
Results
TGF-β2/ATX ratio was significantly high in AH of control or POAG compared with SOAG, and negatively correlated with IOP. RNA scope revelated positive expressions of both TGF-β2 and ATX in ciliary body (CB) and TM in control, but ATX expressions was significantly enhanced in SOAG. In hTM cells, ATX expressions were regulated by TGF-β2 with concentration-dependent manner. In counter, ATX also induced TGF-β1, TGF-β2 and TGFBI upregulations and activation of the Smad-sensitive promoter, as well as upregulation of fibrotic markers, and these upregulation was significantly suppressed by both TGF-β and ATX inhibition.
Conclusions
Trans-signaling of TGF-β2 regulates ATX expressions and thereby induced upregulations of TGF-βs or fibrosis of hTM. TGF-β2 trans-signaling potently regulate ATX transcription and signaling in hTM cells, which may reflect different profile of these mediators in glaucoma subtypes. - 中文關鍵字:
- 英文關鍵字: Transforming Growth factor β, Autotaxin, Glaucoma, Human trabecular meshwork