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Sandrine LE ROUX, Peter Boman, Patrik Danielson, neuropeptide group; TGF-β1 modulates the functional expression of the NK-1 receptor in human corneal fibroblasts. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5228.
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Transforming growth factor beta 1 (TGF-β1) is a cytokine involved in a variety of processes, such as differentiation of fibroblasts into myofibroblasts. TGF-β1 has also been shown to delay the internalization of the Neurokinin-1 receptor (NK-1 R) after its activation by its ligand, the neuropeptide substance P (SP). NK-1 R comprises two naturally occurring variants, a full-length and a truncated form, triggering different cellular responses. SP has been shown to be involved in important events in the cornea essential for the proper organization of collagen fibers and the transparency of the stroma. An impaired signaling through NK-1 R could thus disturb the extracellular matrix and impact the vision quality. We hypothesize that TGF-β1 modulates the expression pattern and function of the NK-1 R in human corneal fibroblasts. The purpose of this study was to test that hypothesis.
Cultures of primary corneal fibroblasts were set-up with cells derived from healthy corneas, obtained from donated transplantation graft leftovers. Immunocytochemistry for the TGF-β receptor type I (TGF-βRI) and NK-1 R was performed. Gene expression was assessed with qPCR. Western blot was used to confirm the gene expression results at the protein level.
Expression of TGF-βRI was confirmed on corneal stromal derived fibroblasts. Treating the fibroblasts with TGF-β1 significantly reduced the expression of the NK-1 R gene. Furthermore, immunocytochemistry for NK-1 R showed that the full-length version of the receptor is reduced after treatment by TGF-β1 (figure).
TGF-β1 downregulates the gene expression of NK-1 R in human corneal fibroblasts, and the results also suggest that it disturbs the signaling pathways triggered by the receptor by reducing the full-length version of it, which might explain the delay in internalization after activation by SP seen with TGF-β1 treatment.
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