| Summary: | 碩士 === 國防醫學院 === 病理及寄生蟲學研究所 === 101 === Autoimmune crescentic glomerulonephritis (ACGN) is a progressive form of glomerulonephritis, in which extensive glomerular crescents and macrophages/lymphocytes infiltrations are formed. However, the current therapy for ACGN is still poor, and many patients require dialysis or renal transplantation. Recent studies have demonstrated that transcription factor Kruppel-Like Factor 2 (KLF2) regulates the expression of genes involved in regulation of vascular tone, inflammation, migration and morphology. Meanwhile, KLF2 is greatly increased in glomerular endothelial cell in response to laminar shear stress, and also is as a negative regulator of monocytic activation through inhibiting the activation of NF-KB pathway. In the present study, we tested the hypothesis that KLF2 gene therapy might prevent the progression of ACGN mice by enhancing the KLF2 pathway, inhibiting renal T cell/macrophage infiltration, and blocking the NF-κB mediated inflammatory pathway. We delivered KLF2 plasmids into the kidney of ACGN mice, using a kidney-targeting ultrasound-mediated microbubble inducible gene transfer. The results showed that KLF2 gene therapy significantly inhibited renal injury including: (1) proteinuria and renal function impairment; (2) renal fibrosis such as glomerular sclerosis, tubulointerstitial collagen matrix expression, and renal macrophage infiltration. Further study demonstrated that improved ACGN renal injury by overexpression of KLF2 was associated with a significant activation of KLF2 signaling pathway, and inhibition of NF-κB signaling pathways locally in the kidney.
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