Tissue inhibitor of metalloproteinase-1 (TIMP-1) plays various roles in cell growth in different cell types. However, few studies have focused on TIMP-1's effect on fibroblast cells. In this study, we investigated the effects of TIMP-1 overexpression on NIH3T3 fibroblast proliferation and potential transduction signaling pathways involved. Overexpression of TIMP-1, by transfection of the pLenti6/V5-DESTTIMP-1 plasmid, significantly promoted NIH3T3 proliferation as determined by the BrdU array. Neither 5 nor 15 nM GM6001 (matrix metalloproteinase system inhibitor) affected NIH3T3 proliferation, but 45 nM GM6001 inhibited proliferation. TIMP-1 overexpression activated the p-Akt pathway, but not the p-ERK or p-p38 pathway. In TIMP-1-transfected cells, cyclinD1 was upregulated and p21CIP1 and p27(KIP1) were downregulated, which promoted cell entry into the S and G2/M phases. The PI3-K inhibitor LY294002 abolished the TIMP-1-induced effects. Overexpression of intracellular TIMP-1 stimulated NIH3T3 fibroblast proliferation in a matrix metalloproteinase (MMP)-independent manner by activating the p-Akt pathway and related cell cycle progression.
Chronic kidney disease (CKD) has been a global health problem that has a great possibility of being developed into uremia in the end. Hemodialysis (HD) is the most commonly used strategy for treating uremic patients; however, the patients still have a high risk of suffering various complications. It is well recognized that lipid disorder usually occurs in maintenance HD patients. To systemically study the effects of HD on lipid metabolism associated with uremia, we employed an ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based lipidomics method. A total of 87 human plasma samples from patients with prehemodialysis (pre-HD)/posthemodialysis (post-HD) treatment and the healthy controls were enrolled in the study. As compared with pre-HD patients, many plasma lipids showed significant changes (p < 0.05) in patients receiving HD therapy. Specifically, sum of free fatty acids (FFA) as well as saturated FFA and eicosanoids and sums of lyso-phosphatidylinositols and lyso-phosphatidylethanolamines, FFA 16:1/FFA 16:0, and FFA 18:1/FFA 18:0 were obviously higher in the pre-HD group than in the controls while they were significantly lower in patients after HD. These results indicated that UPLC-Q-TOF/MS-based lipidomics is a promising approach to investigate lipid alterations in relation to uremia and it is helpful to understand complex complications involved in HD patients.
The study explored the characteristics and correlation factors of transformation in subclasses of class IV lupus nephritis. Patients with class IV lupus nephritis were subjected to repeat biopsies after 6 months of induction treatment. Transformation rate between two subclasses, class IV-S and class IV-G, was compared. Influence Factors of transformation were evaluated. Class IV-G had more severe hypertension and higher score of immunofluorescence index, glomerular active lesions, tubular and vascular lesions. Class IV-S had a higher percentage of glomerular fibrinoid necrosis. Class IV-S appeared a higher rate of transformation to class II than class IV-G (57% vs. 27%). In each subclass, active lesion also showed a higher rate of transformation to class II than active/chronic lesion (IV-G: 41.2% vs. 12.5%; IV-S: 71.4% vs. 42.8%). Patients who maintained class IV had higher blood pressure, obvious proteinuria, declined kidney function, and lower C3 level. Immunosuppressive therapy, urine protein, and vascular lesions were independent risk factors for the pathologic transformation. The rate of transformation in class IV-S was higher than that in class IV-G. The transformation is most likely to benefit from immunosuppressive therapy. Urine protein and vascular lesions are correlated with the transformation in class IV lupus nephritis.
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