ABSTRACT
ObjectiveTo explore the effects of eukaryotic translation initiation factor 6 (eIF6) on the expression of fibrotic cy tokines and metabolic enzymes derived from M2 macrophages. MethodseIF6 wild type mice (eIF6+/+) and eIF6 knock out mice (eIF6+/-) were used. Macrophages were collected from peritoneal lavage fluid, and they were stimulated with IL-4 for enrichment of M2 macrophages. The differential gene expressions of eIF6+/+ and eIF6+/- M2 macrophages were studied with gene chip. The differential expression of genes was further confirmed with both RT-PCR and ELISA. ResultsThe gene chip showed that the expressions of VEGF and TIMP-2 were down-regulated in eIF6+/+ macrophages compared with those in eIF6+/- M2 macrophages, while the expression of MMP-2 was up-regulated in eIF6+/+ M2 macrophages (P<0.05). The result of RT-PCR and ELISA had confirmed that the RNA and protein expressions of VEGF and TIMP-2 were decreased in eIF6+/+ macrophages compared with those in eIF6+/- M2 macrophages, while the RNA and protein expressions of MMP-2 were up-regulated in eIF6+/+ M2 macrophages (P<0.05). ConclusioneIF6 not only inhibits the expression of VEGF, reduces angiogenesis and granulation tissue formation, but also enhances the extracellular matrix degradation and deposition by regulating the balance of MMP2/TIMP2, and thus attenuating the degree of fibrosis (scar formation).
ABSTRACT
Objective To investigate the possible role of eukaryotic initiation factor 6(eIF6)in the development of kidney inter-stitial tissue fibrosis in a mouse model of unilateral ureteral obstruction(UUO).Methods (1)UUO model was set up in eIF6+/-and eIF6+/+ mice.(2)HE and Masson staining were used to histologically assess the interstitial deposition of collagen in mouse kidney.Immunohistochemistry and image analysis were applied to analyze the expression of α-SMA and TGF-β1 in mouse kidney as well as eIF6 in human kidney samples.Results 10 days after unilateral ureteral obstruction,more kidney interstitial fibrosis tissues were found in eIF6+/- mice than that in eIF6+/+ mice.TGF-β1 andα-SMA were expressed more intensive in tubular epithelial cells of eIF6+/- mice than that of eIF6+/+ mice in the UUO model.Expression of eIF6 is lower in the region of fibrosis than that in non-fibrotic area.Conclusion eIF6 might be involved in the development of kidney interstitial tissue fibrosis by regulating the expres-sion of TGF-β1 .