Effects of transforming growth factor-β2 on myocilin expression and secretion in human primary cultured trabecular meshwork cells.
نویسندگان
چکیده
High intraocular pressure (IOP) is a risk factor for primary open-angle glaucoma (POAG). The trabecular meshwork (TM), a reticular tissue in the outflow passage of the aqueous humor (AH), is a major contributor to intraocular outflow resistance. High levels of myocilin (MYOC), which is expressed in the TM, are associated with high IOP. Furthermore, transforming growth factor-β2 (TGF-β2) concentrations in human AH are significantly elevated in POAG patients. This study was designed to investigate the effects of TGF-β2 on MYOC expression and secretion in human primary cultured TM cells. Primary cultured human TM cells were treated with 0 (control group), 1, 10, and 100 ng/mL TGF-β2 for 12, 24, or 48 h. MYOC mRNA and protein expressions in TM cells and protein secretion in conditioned media were analyzed by semi-quantitative RT-PCR, Western blotting, and enzyme-linked immunosorbent assays (ELISA), respectively. TM cells treated with 1, 10, and, 100 ng/mL TGF-β2 for 48 h showed higher MYOC mRNA and protein expressions than those in the control group (0 ng/mL TGF-β2) (all P < 0.05). Treatment with TGF-β2 for 48 h also induced MYOC secretion in conditioned media in a dose-dependent manner (0 ng/mL: 7.107±1.163 pg/ml; 1 ng/mL: 7.879±1.894 pg/ml; 10 ng/mL: 8.063±1.181 pg/ml; 100 ng/mL: 8.902±0.699 pg/ml; all P < 0.05). In Conclusion, TGF-β2 induced MYOC expression and secretion in human primary cultured TM cells. Further investigations are required to confirm the involvement of these two factors in POAG pathogenesis.
منابع مشابه
Modulation of myocilin/TIGR expression in human trabecular meshwork.
PURPOSE To study factors that modulate myocilin/trabecular meshwork inducible glucocorticoid response protein (TIGR) mRNA expression in human trabecular meshwork (TM). METHODS mRNA from fresh TM of four human donors, from perfused anterior segment organ cultured TM of three donors, and from four primary TM cell lines of different donors was isolated. The full length cDNA of myocilin/TIGR was ...
متن کاملp38 MAP Kinase Inhibitor Suppresses Transforming Growth Factor-β2–Induced Type 1 Collagen Production in Trabecular Meshwork Cells
Glaucoma is an age-related neurodegenerative disease of retinal ganglion cells, and appropriate turnover of the extracellular matrix in the trabecular meshwork is important in its pathology. Here, we report the effects of Rho-associated kinase (ROCK) and p38 MAP kinase on transforming growth factor (TGF)-β2-induced type I collagen production in human trabecular meshwork cells. TGF-β2 increased ...
متن کاملTRANSFORMING GROWTH FACTOR β2 UP-REGULATES GM-CSF GENE IN HUMAN BLADDER CARCINOMA CELL LINE HTB 5637
Transforming growth factor betas are multifunctional polypeptides in the cytokine superfamily. They have a growth inhibitory role on hemopoietic progenitor cells in semisolid colony assay as well as in long-term bone-marrow culture. TGF - β2 represses stromal cells, stem cell factor gene transcription, and decreases the stability of c-kit transcripts in hemopoietic cells. TGF-β also modulat...
متن کاملReversal of mutant myocilin non-secretion and cell killing: implications for glaucoma.
Glaucoma is a progressive blinding disease characterized by gradual loss of vision due to optic neuropathy and retinal ganglion cell death. Increased intraocular pressure is a common feature of glaucoma that is thought to arise from an increased resistance to outflow of aqueous humor through the trabecular meshwork. Mutations of the myocilin gene are one cause of autosomal dominant juvenile- an...
متن کاملSmad7 siRNA inhibit expression of extracellular matrix in trabecular meshwork cells treated with TGF-β2
PURPOSE Extracellular matrix (ECM) deposits lead to elevated resistance of aqueous humor outflow which play an important role in the development of primary open angle glaucoma (POAG). The TGF-β2 (transforming growth factor β)/Smad (signaling mathers against decapentaplegic) pathway is known to regulate the ECM deposits. In this study, we determined the effect of Smad7 siRNA transfection in inhi...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- International journal of clinical and experimental pathology
دوره 7 8 شماره
صفحات -
تاریخ انتشار 2014