The phospholipid analogue hexadecylphosphocholine (HePC) inhibits proliferation of keloid fibroblasts in vitro and modulates their fibronectin and integrin synthesis
ARCHIVES OF DERMATOLOGICAL RESEARCH
Authors: BlumePeytavi, U; Geilen, CC; Sommer, C; AlmondRoesler, B; Orfanos, CE
Abstract
Hexadecylphosphocholine (HePC), a topically effective compound, exerts a strong antiproliferative effect on neoplastic cells, In the present study we investigated (I) the antiproliferative effect of HePC on benign mesenchymal cells in vitro, using as examples normal and keloid fibroblasts, and (2) the influence of HePC on various functional properties of these cells, including phosphatidylcholine biosynthesis, their capacity to reorganize a three-dimensional collagen-I matrix, and their expression and synthesis of fibronectin and subunits of the beta(1) integrin family, Fibroblasts derived from keloids (kelfib) and from normal skin (nfib) mere cultured in serum-containing medium and treated in the third passage with 50 mu mol/l HePC, Proliferative activity was significantly (P < 0.05) more strongly inhibited in kelfib than in nfib under HePC treatment, whereas their phosphatidylcholine synthesis was inhibited to a similar extent, However, the ability of fibroblasts to contract a three-dimensional collagen-I lattice was significantly (P < 0.05) enhanced only in kelfib treated with HePC, These functional differences following treatment with HePC were paralleled by an upregulation of the alpha(2)- and beta(1)-integrin chains, and a downregulation of fibronectin synthesis and the alpha(5)-subunit, Our results indicate a differential modulation of kelfib metabolism by HePC, suggesting a possible new therapeutic approach for keloid and hypertrophic scars in vivo.
Absence of the Transcription Factor Nfib Delays the Formation of the Basilar Pontine and Other Mossy Fiber Nuclei
JOURNAL OF COMPARATIVE NEUROLOGY
Authors: Kumbasar, Asli; Plachez, Celine; Gronostajski, Richard M.; Richards, Linda J.; Litwack, E. David
Abstract
Transcription factors of the Nuclear Factor I (Nfi) family are important for the development of specific neuronal and glial populations in the nervous system. One such population, the neurons of the basilar pontine nuclei, expresses high levels of Nfi proteins, and the pontine nuclei are greatly reduced in mice lacking a functional Nfib gene. Pontine neurons, along with other precerebellar neurons that populate the hindbrain, arise from precursors in the lower rhombic lip and migrate anteroventrally to reach their final location. Using immunohistochemistry, we find that NFI-B expression is specific for mossy fiber populations of the precerebellar system. Analysis of the Nfib(-/-) hindbrain indicates that the development of the basilar pontine nuclei is delayed, with pontine neurons migrating 1-2 days later than in control animals, and that significantly fewer pontine neurons are produced. While the mossy fiber nuclei of the caudal medulla do form, they also exhibit a developmental delay. Nfia and Nfix null mice exhibit no apparent pontine phenotype, implying specificity in the action of NFI family members. Collectively, these data demonstrate that Nfib plays an important role in the generation of precerebellar mossy fiber neurons, and may do so at least in part by regulating neurogenesis. J. Comp. Neurol. 513:98-112, 2009. (C) 2008 Wiley-Liss, Inc.