ABSTRACT
OBJECTIVE: This study aims to elucidate the role of Kruppel-like factor (KLF5) and myxovirus resistance 1 (MX1) in the progression of renal fibrosis in lupus nephritis (LN). METHODS: First, the expression of KLF5 and MX1 was assessed in the peripheral blood of LN patients and healthy participants. Next, the pathological changes in renal tissues were evaluated and compared in BALB/c and MRL/lpr mice, by detecting the expression of fibrosis marker proteins (transforming growth factor-ß [TGF-ß] and CTGF) and α-SMA, the content of urine protein, and the levels of serum creatinine, blood urea nitrogen, and serum double-stranded DNA antibody. In TGF-ß1-induced HK-2 cells, the messenger RNA levels of KLF5 and MX1 were tested by qRT-PCR, and the protein expression of α-SMA, type I collagen (Col I), fibronectin (FN), and matrix metalloproteinase 9 (MMP9) was measured by western blot analysis. Moreover, the relationship between KLF5 and MX1 was predicted and verified. RESULTS: In renal tissues of MRL/lpr mice and the peripheral blood of LN patients, KLF5 and MX1 were highly expressed. Pearson analysis revealed that KLF5 was positively correlated with MX1. Furthermore, KLF5 bound to MX1 promoter and promoted its transcription level. MRL/lpr mice showed substantial renal injury, accompanied by increased expression of α-SMA, TGF-ß, CTGF, Col I, FN, and MMP9. Injection of sh-KLF5 or sh-MX1 alone in MRL/lpr mice reduced renal fibrosis in LN, while simultaneous injection of sh-KLF5 and ad-MX1 exacerbated renal injury and fibrosis. Furthermore, we obtained the same results in TGF-ß1-induced HK-2 cells. CONCLUSION: Knockdown of KLF5 alleviated renal fibrosis in LN through repressing the transcription of MX1.
Subject(s)
Lupus Nephritis , Matrix Metalloproteinase 9 , Animals , Mice , Fibrosis , Lupus Nephritis/genetics , Matrix Metalloproteinase 9/genetics , Mice, Inbred MRL lpr , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/geneticsABSTRACT
AIM: IgA nephropathy is virtually known as the most common glomerulopathy to end-stage renal failure in the world. Mycophenolate mofetil is a selective immunosuppressant widely used in organ transplantation, yet its tolerance and effectiveness in IgAN is controversial. METHODS: This is a systematic review and random-effects meta-analysis, searching PubMed, Embase, Te Cochrane Library, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature and Chinese Science and Technology Periodicals. Screen out randomized controlled trials on patients with biopsy-proven IgA nephropathy and analysis mycophenolate mofetil treatment regimens used for therapy of IgA nephropathy. Complete remission and partial remission, doubling of creatinine level, proteinuria, incidence of end-stage kidney disease, infection, Cushing syndrome, diabetes, hepatic dysfunction or gastrointestinal symptoms, neurologic or visual ambiguity, acne, and alopecia were observed. RESULTS: Nine relevant trials were conducted with 587 patients enrolled. In Mycophenolate mofetil or plus medium/low-dose steroid comparing full-dose steroid alone or placebo, there was no significant difference. The risk of Cushing syndrome and diabetes had been significantly lowered with Mycophenolate mofetil-treated patients, while the risk of infection had been increased. CONCLUSIONS: Mycophenolate mofetil therapy did not differ in reducing proteinuria and Scr in patients with IgAN who had persistent proteinuria, while having fewer Cushing syndrome and diabetes risk and more infection risk. However, larger randomized studies are needed to reveal these results.
