Polyunsaturated fatty acid regulation of collagen formation in 3T3 Swiss fibroblasts
Proper collagen formation is essential to optimal wound healing but undesirable formation develops into collagen related diseases. A better understanding of the regulation of fibroblast collagen formation will unravel the complex mechanisms in wound healing and diseases. Since PUFA enrichments can change the fibroblast collagen formation differently, a polyunsaturated fatty acids (PUFA)-treated 3T3-Swiss fibroblast model was developed. As the ratio of n-6 to n-3 PUFA enrichments increased, total n-6 fatty acids composition increased but the collagen formation decreased in 3T3-Swiss fibroblasts. Previous experiments about the activation of prostaglandins E2 (PGE2) and collagen formation raised the hypothesis that different PUFA altered collagen formation was associated to the various responses of PGE2 signaling pathways. Decreased collagen formation in n-6 PUFA treated fibroblasts is associated to the enhanced PGE2 producation and the activation of EP1, EP2 and EP4 receptor subtypes and correlated second messengers, while n-3 PUFA treated cells increased the collagen formation by decreasing PGE2 producation and the activation of EP2 and EP4 receptors. Nuclear factor-kappa B (NF-κB) pathway activates some collagen-related cytokines. Gene profiling experiments of many NF-κB pathway-related genes in n-3 PUFA reated fibroblasts were more responsive to the activation and the inhibition of NF-κB pathway than those in n-6 PUFA-treated fibroblasts. The PGE2 and NF-κB signaling pathways were linked by inducible nitric oxide synthase (iNOS) and nitric oxide (NO). An in vitro wound by inducible nitric oxide synthase (iNOS) and nitric oxide (NO). An in vitro wound healing model verified the relationships between the collagen formation regulation mechanisms and wound healing. Activation of NF-κB pathway increased the iNOS expression, NO and PGE2 production, collagen formation, and wound healing. When stimulating the NF-κB signaling pathway, n-3 PUFA treated fibroblasts had more iNOS mRNA expression, collagen formation and wound healing, but less NO and PGE2 production than n-6 PUFA enriched cells. In conclusion, the PUFA altered fibroblasts collagen formation can be reglated by the PGE2 and NF-κB signaling pathways, which have the cross-talk of iNOS and NO. Future in vivo studies are necessary to confirm these results and provide the potential clinical uses of PUFA as adjunctive theripes in wound tissue healing and collagen formation related diseases.
Turek, Purdue University.
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