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Sarah E Nicholas, Tyler Rowsey, Megan Stiles, Sufiya khanam, Nawajes A Mandal, Dimitrios Karamichos; Sphingolipids and TGF-β signaling in the human cornea. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1266.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal fibrosis leaves the cornea opaque and can result in partial or complete vision loss for which the only current treatment is corneal transplantation. Recently sphingolipids (SPL) have been linked to corneal fibrosis and found to be modulated by the transforming growth factor-β (TGF-β) pathway. The aim of this study is to dissect the role of sphingolipids in corneal fibrosis and their signaling mechanisms related to the three TGF-β isoforms.
Healthy human corneal fibroblasts (HCFs) were cultured in EMEM with 10% FBS and 0.5mM 2-O-α-D-glucopyranosyl-L-ascorbic acid in 3D constructs and allowed to grow for 4 weeks in the presence of 0.1ng/mL TGF-β1, TGF-β2, and TGF-β3. Cultures without any growth factors served as Controls. After 4 weeks the cultures were examined for the expression of sphingolipid specific pathway signaling using Real-Time PCR and Western Blot.
We investigated all five sphingosine-1-phosphate receptors 1 through 5. TGF-β1 and TGF-β3 led to significant upregulation of sphingosine-1-phosphate receptor 3 (S1PR3) when compared to Control HCFs. TGF-β2 did not modulate S1PR3. TGF-β2, on the other hand, led to significant upregulation of sphingosine kinase 1 (SphK1), while TGF-β3 resulted in upregulation of SphK2.
Overall, we have drawn some intriguing signaling cross talk between sphingolipid molecules and TGF-β isoforms in human corneal fibroblasts. This study suggests that TGF-β3 driven upregulation of S1PR3 may represent a novel target in regulating corneal fibrosis. Future studies will dissect the signaling mechanism further.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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