Quantitative proteomics: TGF?? signaling in trabecular meshwork cells.

ABSTRACT: Transforming growth factor beta 2 (TGF??) is often elevated in the aqueous humor (AH) and trabecular meshwork (TM) of patients with primary open-angle glaucoma (POAG) and appears to contribute to POAG pathogenesis. To better understand TGF?? signaling in the eye, TGF??-induced proteomic changes were identified in cells cultured from the TM, a tissue involved in intraocular pressure (IOP) elevation in glaucoma.Primary cultures of human TM cells from four donors were treated with or without TGF?? (5 ng/mL) for 48 hours; then cellular protein was analyzed by liquid chromatography-mass spectrometry iTRAQ (isobaric tags for relative and absolute quantitation) technology.A total of 853 proteins were quantified. TGF?? treatment significantly altered the abundance of 47 proteins, 40 of which have not previously been associated with TGF?? signaling in the eye. More than half the 30 elevated proteins support growing evidence that TGF?? induces extracellular matrix remodeling and abnormal cytoskeletal interactions in the TM. The levels of 17 proteins were reduced, including four cytoskeletal and six regulatory proteins. Both elevated and decreased regulatory proteins implicate TGF??-altered processes involving transcription, translation, and the glutamate/glutamine cycle. Altered levels of eight mitochondrial proteins support TGF??-induced mitochondrial dysfunction in the TM that in POAG could contribute to oxidative damage in the AH outflow pathway, TM senescence, and elevated IOP.The results expand the repertoire of proteins known to participate in TGF?? signaling, provide new molecular insight into POAG, and establish a quantitative proteomics database for the TM that includes candidate glaucoma biomarkers for future validation studies.

SUBMITTER: Bollinger KE 

PROVIDER: S-EPMC3208113 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature