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S. Basavanthappa, G. Romeo, A. Venkatakrishnan, A. Kazlauskas; A PDGF–CC/PDGF alpha receptor autocrine loop require Src to elevate collagen 1 mRNA; implication in experimental PVR. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4605.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To test the hypothesis that the difference in the Proliferative Vitreoretinopathy(PVR) potential of the α and ß Platelet derived growth factor (PDGF) relates to their capacity to promote collagen 1. Methods: Collagen 1 mRNA levels were determined by northern blotting in cells expressing the PDGF α receptor (αPDGFR), the PDGF ß(ßPDGFR) or α PDGFR signaling mutants. Collagen protein level was measured by [3H] Proline incorporation. PDGF–C mRNA and PDGF–CC protein levels were determined by Northern and western blotting respectively. The level of PDGF–CC was reduced by stably expressing a PDGF–C siRNA. PDGFR and Src levels were measured by Western blotting. Results: The αPDGFR increased basal collagen 1 mRNA levels to a much greater extent than the ßPDGFR. Endogenous production of PDGF–CC was necessary for the rise in collagen 1 mRNA levels in αPDGFR expressing cells. There was a large variation in ability of α PDGFR signaling mutants to elevate collagen 1 mRNA, which did not correlate with the PVR potential. The αPDGFR acted through Src family kinases (SFKs) to elevate collagen 1 mRNA. Conclusions:Our data do not support the hypothesis that differences in collagen 1 mRNA levels explain the unequal PVR potential of the two PDGFRs. The capacity of the αPDGFR to elevate collagen 1 mRNA was largely due to an autocrine relationship of the αPDGFR with PDGF–CC. Finally, SFKs are one of the intracellular effectors of the αPDGFR needed to elevate collagen 1 mRNA.
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