Systemic administration of naked plasmid encoding HGF attenuates puromycin aminonucleoside-induced damage of murine glomerular podocytes

2011 ◽  
Vol 301 (4) ◽  
pp. F784-F792 ◽  
Author(s):  
Xuan Bu ◽  
Yang Zhou ◽  
Hua Zhang ◽  
Wenjing Qiu ◽  
Lu Chen ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Gene Transfection ◽  
Systemic Administration ◽  
Renal Diseases ◽  
Puromycin Aminonucleoside ◽  
Podocyte Injury ◽  
Rapid Injection ◽  
Naked Plasmid

Podocyte injury is considered to play important roles in the pathogenesis of human glomerular disease. There is accumulating evidence suggesting that hepatocyte growth factor (HGF) elicits preventive activity for glomerular cells in animal models of chronic renal diseases. In this study, we demonstrated that delivery of a naked plasmid vector encoding the human HGF gene into mice by a hydrodynamic-based in vivo gene transfection approach markedly reduced proteinuria and attenuated podocyte injury in a mouse model induced by puromycin aminonucleoside (PAN) injection. Systemic administration by rapid injection via the tail vein of a naked plasmid containing HGF cDNA driven under a cytomegalovirus promoter (pCMV-HGF) produced a remarkable level of human HGF protein in the circulation. Tissue distribution studies suggested that the kidney expressed a high level of the HGF transgene. Meanwhile, compared with tubules and interstitium, a higher level of exogenous HGF protein was detected in the glomeruli. Administration of pCMV-HGF dramatically abated the urine albumin excretion and podocyte injury in PAN nephropathy in mice. Exogenous expression of HGF produced evidently beneficial effects, leading to restoration of Wilms' tumor-1 (WT1) and α-actinin-4 expression and attenuation of ultrastructural damage of the podocytes. In vitro, HGF not only restored WT1 and α-actinin-4 expression but also inhibited albumin leakage of podocytes incubated with PAN in a Transwell culture chamber. These results suggest that HGF might provide a novel strategy for amelioration of podocyte injury.

Adrenomedullin ameliorates podocyte injury induced by puromycin aminonucleoside in vitro and in vivo through modulation of Rho GTPases

2017 ◽  
Vol 49 (8) ◽  
pp. 1489-1506 ◽  
Author(s):  
Nan Dong ◽  
Lixia Meng ◽  
Ruqun Xue ◽  
Meng Yu ◽  
Zhonghua Zhao ◽  
...  
Keyword(s):  
Rho Gtpases ◽  
Puromycin Aminonucleoside ◽  
Podocyte Injury

scholarly journals Contribution of TGF-β1 and Effects of Gene Silencer Pyrrole-Imidazole Polyamides Targeting TGF-β1 in Diabetic Nephropathy

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 950 ◽  
Author(s):  
Shu Horikoshi ◽  
Noboru Fukuda ◽  
Akiko Tsunemi ◽  
Makiyo Okamura ◽  
Masari Otsuki ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Target Genes ◽  
Mesangial Cells ◽  
Diabetic Rats ◽  
Histological Evaluation ◽  
Renal Diseases ◽  
Podocyte Injury ◽  
Tgf Β1

TGF-β1 has been known to induce diabetic nephropathy with renal fibrosis and glomerulosclerosis. DNA-recognized peptide compound pyrrole-imidazole (PI) polyamides as novel biomedicines can strongly bind promoter lesions of target genes to inhibit its transcription. We have developed PI polyamide targeting TGF-β1 for progressive renal diseases. In the present study, we evaluated the contribution of TGF-β1 in the pathogenesis of diabetic nephropathy, and examined the effects of PI polyamide targeting TGF-β1 on the progression of diabetic nephropathy in rats. For in vitro experiments, rat renal mesangial cells were incubated with a high (25 mM) glucose concentration. Diabetic nephropathy was established in vivo in eight-week-old Wistar rats by intravenously administering 60 mg/kg streptozotocin (STZ). We examined the effects of PI polyamide targeting TGF-β1 on phenotype and the growth of mesangial cells, in vitro, and the pathogenesis of diabetic nephropathy in vivo. High glucose significantly increased expression of TGF-β1 mRNA, changed the phenotype to synthetic, and increased growth of mesangial cells. STZ diabetic rats showed increases in urinary excretions of protein and albumin, glomerular and interstitial degenerations, and podocyte injury. Treatment with PI polyamide targeting TGF-β1 twice weekly for three months improved the glomerular and interstitial degenerations by histological evaluation. Treatment with PI polyamide improved podocyte injury by electron microscopy evaluation. These findings suggest that TGF-β1 may be a pivotal factor in the progression of diabetic nephropathy, and PI polyamide targeting TGF-β1 as a practical medicine may improve nephropathy.

miR-499 Ameliorates Podocyte Injury by Targeting Calcineurin in Minimal Change Disease

2018 ◽  
Vol 47 (2) ◽  
pp. 94-102 ◽  
Author(s):  
Kaiyue Zhang ◽  
Wenjuan Sun ◽  
Lai Zhang ◽  
Xuefang Xu ◽  
Jidong Wang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Minimal Change Disease ◽  
Calcineurin Inhibitors ◽  
Current Treatment ◽  
Minimal Change ◽  
Puromycin Aminonucleoside ◽  
Podocyte Injury ◽  
Novel Strategy

Background: Podocyte injury is a hallmark of minimal change disease (MCD). Calcineurin inhibitors have been widely used in the current treatment of MCD, and miR-499 may target calcineurin. We aimed to study the function of miR-499 in MCD and test whether miR-499 delivery can improve MCD. Methods: An MCD mouse model was generated using puromycin aminonucleoside (PAN). MiR-499 was delivered using lentiviruses. Biochemical indicators including serum albumin, triglyceride, cholesterol, and 24-h urine protein were determined. Targets of miR-499 were confirmed using reporter gene activity assays. The ultrastructure of podocytes was analyzed using transmission electron microscopy. Results: MiR-499 significantly improved MCD-related symptoms and signs. Foot-process effacement was caused by PAN and partially reversed by miR-499. We identified that both CnAα and CnAβ were targets of miR-499, and were overexpressed in the presence of PAN. However, miR-499 reduced the expression of CnAα and CnAβ, leading to a decreased activity of calcineurin signaling in mouse podocytes in vitro and in vivo. In addition, miR-499 recovered PAN-induced reduction of cell viability. Conclusions: MiR-499 ameliorated podocyte injury by targeting CnAα and CnAβ in a PAN-induced MCD mouse model. Delivery of miR-499 can be a novel strategy for MCD treatment.

Non-Viral Vectors for Gene Delivery

2018 ◽  
Vol 9 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Aparna Bansal ◽  
Himanshu
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Gene Transfection ◽  
Expression System ◽  
Target Cells ◽  
Specific Expression ◽  
Naked Dna

Introduction: Gene therapy has emerged out as a promising therapeutic pave for the treatment of genetic and acquired diseases. Gene transfection into target cells using naked DNA is a simple and safe approach which has been further improved by combining vectors or gene carriers. Both viral and non-viral approaches have achieved a milestone to establish this technique, but non-viral approaches have attained a significant attention because of their favourable properties like less immunotoxicity and biosafety, easy to produce with versatile surface modifications, etc. Literature is rich in evidences which revealed that undoubtedly, non–viral vectors have acquired a unique place in gene therapy but still there are number of challenges which are to be overcome to increase their effectiveness and prove them ideal gene vectors. Conclusion: To date, tissue specific expression, long lasting gene expression system, enhanced gene transfection efficiency has been achieved with improvement in delivery methods using non-viral vectors. This review mainly summarizes the various physical and chemical methods for gene transfer in vitro and in vivo.

Retracted Article: A multifunctional self-dissociative polyethyleneimine derivative coating polymer for enhancing the gene transfection efficiency of DNA/polyethyleneimine polyplexes in vitro and in vivo

2015 ◽  
Vol 6 (5) ◽  
pp. 780-796 ◽  
Author(s):  
Cheng Wang ◽  
Xiuli Bao ◽  
Xuefang Ding ◽  
Yang Ding ◽  
Sarra Abbad ◽  
...  
Keyword(s):  
Transfection Efficiency ◽  
Gene Transfection ◽  
Retracted Article ◽  
First Time

A novel coating polymer LPHF is developed for the first time to elevate the transfection efficiency of DP binary polyplexes in vitro and in vivo.

scholarly journals In vitro and in vivo effects of polyethylene glycol (PEG)-modified lipid in DOTAP/cholesterol-mediated gene transfection

2010 ◽  
pp. 371 ◽  
Author(s):  
Hans Skovgaard Poulsen ◽  
Arildsen ◽  
Jack Roth ◽  
Hans Skovgaard Poulsen ◽  
Tuxen Poulsen ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Gene Transfection ◽  
In Vivo Effects

scholarly journals Increased long noncoding RNA maternally expressed gene 3 contributes to podocyte injury induced by high glucose through regulation of mitochondrial fission

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Qiongxia Deng ◽  
Ruowei Wen ◽  
Sirui Liu ◽  
Xiaoqiu Chen ◽  
Shicong Song ◽  
...  
Keyword(s):  
High Glucose ◽  
Noncoding Rna ◽  
Diabetic Kidney Disease ◽  
Mitochondrial Fission ◽  
Diabetic Mice ◽  
Podocyte Injury ◽  
Mitochondrial Translocation ◽  
Maternally Expressed Gene 3

Abstract Excessive mitochondrial fission plays a key role in podocyte injury in diabetic kidney disease (DKD), and long noncoding RNAs (lncRNAs) are important in the development and progression of DKD. However, lncRNA regulation of mitochondrial fission in podocytes is poorly understood. Here, we studied lncRNA maternally expressed gene 3 (Meg3) in mitochondrial fission in vivo and in vitro using human podocytes and Meg3 podocyte-specific knockdown mice. Expression of lncRNA Meg3 in STZ-induced diabetic mice was higher, and correlated with the number of podocytes. Excessive mitochondrial fission of podocytes and renal histopathological and physiological parameters were improved in podocyte-specific Meg3 knockdown diabetic mice. Elongated mitochondria with attenuated podocyte damage, as well as mitochondrial translocation of dynamin-related protein 1 (Drp1), were decreased in Meg3 knockout podocytes. By contrast, increased fragmented mitochondria, podocyte injury, and Drp1 expression and phosphorylation were observed in lncRNA Meg3-overexpressing podocytes. Treatment with Mdivi1 significantly blunted more fragmented mitochondria and reduced podocyte injury in lncRNA Meg3-overexpressing podocytes. Finally, fragmented mitochondria and Drp1 mitochondrial translocation induced by high glucose were reduced following treatment with Mdivi1. Our data show that expression of Meg3 in podocytes in both human cells and diabetic mice was higher, which regulates mitochondrial fission and contributes to podocyte injury through increased Drp1 and its translocation to mitochondria.

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