Eidet, J. R.Reppe, S.Pasovic, L.Olstad, O. K.Lyberg, T.Khan, A. Z.Fostad, I. G.Chen, D. F.Utheim, T. P.2016-04-012016Eidet, J. R., S. Reppe, L. Pasovic, O. K. Olstad, T. Lyberg, A. Z. Khan, I. G. Fostad, D. F. Chen, and T. P. Utheim. 2016. “The Silk-protein Sericin Induces Rapid Melanization of Cultured Primary Human Retinal Pigment Epithelial Cells by Activating the NF-κB Pathway.” Scientific Reports 6 (1): 22671. doi:10.1038/srep22671. http://dx.doi.org/10.1038/srep22671.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318609Restoration of the retinal pigment epithelial (RPE) cells to prevent further loss of vision in patients with age-related macular degeneration represents a promising novel treatment modality. Development of RPE transplants, however, requires up to 3 months of cell differentiation. We explored whether the silk protein sericin can induce maturation of primary human retinal pigment epithelial (hRPE) cells. Microarray analysis demonstrated that sericin up-regulated RPE-associated transcripts (RPE65 and CRALBP). Upstream analysis identified the NF-κB pathway as one of the top sericin-induced regulators. ELISA confirmed that sericin stimulates the main NF-κB pathway. Increased levels of RPE-associated proteins (RPE65 and the pigment melanin) in the sericin-supplemented cultures were confirmed by western blot, spectrophotometry and transmission electron microscopy. Sericin also increased cell density and reduced cell death following serum starvation in culture. Inclusion of NF-κB agonists and antagonists in the culture medium showed that activation of the NF-κB pathway appears to be necessary, but not sufficient, for sericin-induced RPE pigmentation. We conclude that sericin promotes pigmentation of cultured primary hRPE cells by activating the main NF-κB pathway. Sericin’s potential role in culture protocols for rapid differentiation of hRPE cells derived from embryonic or induced pluripotent stem cells should be investigated.en-USJournal Article2016-04-0110.1038/srep22671