Treatment with irbesatan may improve slit diaphragm alterations in rats with adriamycin-induced nephropathy

Wang, Na; Wei, Ri-bao; Li, Ping; Li, Qingping; Xi, Yang; Yang, Yue; Huang, Mengjie; Wang, Rui; Yin, Zhimin; Lv, Yang; Chen, Xiangmei

doi:10.1177/1470320316646884

Cited by 9 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to the well-known hemodynamic effects of inhibiting the renin-angiotensin-aldosterone system (RAAS) ( 215 ), both angiotensin-converting enzyme inhibitor (ACEI) and AngII type 1 receptor blocker (ARB) have shown to significantly increase nephrin expression in murine diabetic models ( 157 , 216 ). A similar effect was also observed in rats models by adriamycin-induced nephropathy and PAN ( 217 , 218 ). Since AngII has a direct TRPC6-mediated calcium signaling ( 219 , 220 ) which results in ROS expression ( 221 ) and proteinuria ( 222 ), inhibiting TRPC6 indirectly via AngII blockade is a feasible strategy in proteinuric diseases such as FSGS.…”

Section: Introductionsupporting

confidence: 77%

Proteinuric Kidney Diseases: A Podocyte's Slit Diaphragm and Cytoskeleton Approach

Nissaisorakarn

Husain

et al. 2018

Front. Med.

View full text Add to dashboard Cite

Proteinuric kidney diseases are a group of disorders with diverse pathological mechanisms associated with significant losses of protein in the urine. The glomerular filtration barrier (GFB), comprised of the three important layers, the fenestrated glomerular endothelium, the glomerular basement membrane (GBM), and the podocyte, dictates that disruption of any one of these structures should lead to proteinuric disease. Podocytes, in particular, have long been considered as the final gatekeeper of the GFB. This specialized visceral epithelial cell contains a complex framework of cytoskeletons forming foot processes and mediate important cell signaling to maintain podocyte health. In this review, we will focus on slit diaphragm proteins such as nephrin, podocin, TRPC6/5, as well as cytoskeletal proteins Rho/small GTPases and synaptopodin and their respective roles in participating in the pathogenesis of proteinuric kidney diseases. Furthermore, we will summarize the potential therapeutic options targeting the podocyte to treat this group of kidney diseases.

show abstract

Section: Introductionsupporting

confidence: 77%

Proteinuric Kidney Diseases: A Podocyte's Slit Diaphragm and Cytoskeleton Approach

Nissaisorakarn

Husain

et al. 2018

Front. Med.

View full text Add to dashboard Cite

show abstract

“…cases, in vitro nephrotoxicity assays are performed by using proximal tubular cells without considering the podocyte that represents, nevertheless, a potential target for drugs. Our model appears to be closed to the functional state of normal human renal cells displaying a selective filtration that could be modulated by nephrotoxic drugs (PAN and ADR) known to induce proteinuria in vivo [16,17]. In addition, the analysis of F-actin distribution and nephrin or ZO-1 expression indicates a good correlation between functional and morphologic events due to treatments with these two drugs.…”

Section: Discussionmentioning

confidence: 85%

Glomerular filtration drug injury: In vitro evaluation of functional and morphological podocyte perturbations

Delézay

Hé

Hodin

et al. 2017

Experimental Cell Research

View full text Add to dashboard Cite

The kidney is an organ that plays a major role in the excretion of numerous compounds such as drugs and chemicals. However, a great number of pharmacological molecules are nephrotoxic, affecting the efficiency of the treatment and increasing morbidity or mortality. Focusing on glomerular filtration, we propose in this study a simple and reproducible in vitro human model that is able to bring to light a functional podocyte injury, correlated with morphologic/phenotypic changes after drug exposure. This model was used for the evaluation of paracellular permeability of FITC-dextran molecules as well as FITC-BSA after different treatments. Puromycin aminonucleoside and adriamycin, compounds known to induce proteinuria in vivo and that serve here as positive nephrotoxic drug controls, were able to induce an important increase in fluorescent probe passage through the cell monolayer. Different molecules were then evaluated for their potential effect on podocyte filtration. Our results demonstrated that a drug effect could be time dependent, stable or scalable and relatively specific. Immunofluorescence studies indicated that these functional perturbations were due to cytoskeletal perturbations, monolayer disassembly or could be correlated with a decrease in nephrin expression and/or ZO-1 relocation. Taken together, our results demonstrated that this in vitro human model represents an interesting tool for the screening of the renal toxicity of drugs.

show abstract

“…Previous studies showed that a tyrosine residue in the nephrin cytoplasmic region could be phosphorylated by Src family kinase Fyn, resulting in interaction between nephrin and podocin, as well as downstream signal pathway enhancement [ 4 ]. Podocin has a hairpin-like structure and embeds in the membrane, interacts with nephrin and CD2AP via cytoplasmic carboxyl terminus, and then mediates connection between SD and podocyte cytoskeleton to stabilize podocytes[ 5 ]. CD2AP is located on the podocyte cytoplasmic side, it can not only adjust cytoskeleton arrangement by connecting directly with F-actin, but also conduct signal transduction by combining directly with nephrin and podocin.…”

Section: Introductionmentioning

confidence: 99%

The protective effect of the EP2 receptor on TGF-β1 induced podocyte injury via the PI3K / Akt signaling pathway

et al. 2018

View full text Add to dashboard Cite

Transforming growth factor β1 (TGF-β1) plays a central role in chronic kidney diseases. TGF-β1 induction causes podocyte injury, which results in proteinuria and renal failure. However, the effect of the prostaglandin E2 /E-prostanoid receptor (EP2) on TGF-β1-induced podocyte injury remains unknown. Previous studies have shown that phosphoinositide 3-OH kinase (PI3K)/Akt is widespread in cells, and is vital for the regulation of cell proliferation, differentiation, apoptosis and metabolism. In this study, we cultured immortalized mouse podocytes in vitro in different groups: control group; TGF-β1 (5ng/ml) group; EP2 agonist Butaprost treatment (10−7, 10−6, or 10-5mol/L) +TGF-β1 group; EP2 antagonist AH6809 treatment (10−7, 10−6, or 10-5mol / L) + TGF-β1 group. We found that compared with the control group, proliferation of podocytes in the TGF-β1 group significantly decreased and apoptosis increased. Expression of cAMP decreased, whereas PGE2 increased. Meanwhile, expressions of nephrin, podocin and CD2AP mRNA and protein were dramatically downregulated, activated caspase-3 was increased, and activated PI3K/Akt activity were depressed. Butaprost intervention promoted podocyte proliferation with reduced apoptosis. Conversely, AH6809 intervention led to opposite results (P<0.05). Our findings suggested that EP2 agonist protects podocytes by increasing expression of cAMP, which creates feedback of inhibiting PGE2 expression. This causes the interaction of nephrin, podocin and CD2AP resulting the inhibition of apoptosis induced by activation of the PI3K / Akt signaling pathway.

show abstract

Treatment with irbesatan may improve slit diaphragm alterations in rats with adriamycin-induced nephropathy

Cited by 9 publications

References 29 publications

Proteinuric Kidney Diseases: A Podocyte's Slit Diaphragm and Cytoskeleton Approach

Proteinuric Kidney Diseases: A Podocyte's Slit Diaphragm and Cytoskeleton Approach

Glomerular filtration drug injury: In vitro evaluation of functional and morphological podocyte perturbations

The protective effect of the EP2 receptor on TGF-β1 induced podocyte injury via the PI3K / Akt signaling pathway

Contact Info

Product

Resources

About