The role of podocyte damage in the etiology of ischemia-reperfusion acute kidney injury and post-injury fibrosis

Chen, Yi; Lin, Liyu; Tao, Xuan; Song, Yankun; Cui, Jiong; Wan, Jianxin

doi:10.1186/s12882-019-1298-x

Cited by 59 publications

(44 citation statements)

References 30 publications

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“…Considering the relevance of podocyte injury to progressive proteinuria previously demonstrated in ischemia-reperfusion and glomerulosclerosis animal models ( Hara et al, 2015 ; Chen et al, 2019 ), we also evaluated whether acute crystalline-related glomerular injury contributes to proteinuria. Indeed, we observed significant albuminuria in treated animals in comparison to the control group.…”

Section: Discussionmentioning

confidence: 99%

“…However, clinical evidence and experimental models of ischemia-reperfusion have revealed that frequently, the recovery of renal function after AKI is incomplete and accompanied by proteinuria, tubular injury and glomerular filtration rate (GFR) decline, leading to end-stage renal disease (ESRD) ( Hingorani et al, 2009 ; Basile et al, 2012 ). Furthermore, other studies using animal models of ischemia-reperfusion and glomerulosclerosis have identified podocyte injury as an etiological factor of progressive proteinuria and kidney function decline ( Hara et al, 2015 ; Chen et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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Sodium Oxalate-Induced Acute Kidney Injury Associated With Glomerular and Tubulointerstitial Damage in Rats

et al. 2020

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Acute crystalline nephropathy is closely related to tubulointerstitial injury, but few studies have investigated glomerular changes in this condition. Thus, in the current study, we investigated the factors involved in glomerular and tubulointerstitial injury in an experimental model of crystalline-induced acute kidney injury (AKI). We treated male Wistar rats with a single injection of sodium oxalate (NaOx, 7 mg•100 g −1 •day −1 , resuspended in 0.9% NaCl solution, i.p.) or vehicle (control). After 24 h of treatment, food and water intake, urine output, body weight gain, and renal function were evaluated. Renal tissue was used for the morphological studies, quantitative PCR and protein expression studies. Our results revealed that NaOx treatment did not change metabolic or electrolyte and water intake parameters or urine output. However, the treated group exhibited tubular calcium oxalate (CaOx) crystals excretion, followed by a decline in kidney function demonstrated along with glomerular injury, which was confirmed by increased plasma creatinine and urea concentrations, increased glomerular desmin immunostaining, nephrin mRNA expression and decreased WT1 immunofluorescence. Furthermore, NaOx treatment resulted in tubulointerstitial injury, which was confirmed by tubular dilation, albuminuria, increased Kim-1 and Ki67 mRNA expression, decreased megalin and Tamm-Horsfall protein (THP) expression. Finally, the treatment induced increases in CD68 protein staining, MCP-1, IL-1β, NFkappaB, and α-SMA mRNA expression, which are consistent with proinflammatory and profibrotic signaling, respectively. In conclusion, our findings provide relevant information regarding crystalline-induced AKI, showing strong tubulointerstitial and glomerular injury with a possible loss of podocyte viability.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sodium Oxalate-Induced Acute Kidney Injury Associated With Glomerular and Tubulointerstitial Damage in Rats

et al. 2020

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“…As a key component of the innate immune response, Toll-like receptors (TLRs) serve to recognize pathogen-associated molecular patterns (PAMPs) that are present on pathogens, and initiate the innate immune response by producing inflammatory cytokines (14,15). In particular, previous studies have shown that TLR2 could be activated in mice using LPS stimulation, which contribute to the development of septic AKI by enhancing inflammatory cytokine production via the NF-κB signaling pathway (14–19). Histological evaluation has demonstrated that TLR2 overactivation in AKI is mainly identified in podocytes, which may be indicative of the important roles podocytes serve in septic AKI pathogenesis (17).…”

Section: Introductionmentioning

confidence: 99%

Treatment with toll‑like receptor 2 inhibitor ortho‑vanillin alleviates lipopolysaccharide‑induced acute kidney injury in mice

et al. 2019

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Reducing inflammation is a promising approach for the prevention and treatment of septic acute kidney injury (AKI), since AKI is characterized by excessive inflammation in the kidney. Previous studies have demonstrated that toll-like receptor 2 (TLR2) is overstimulated, which promotes inflammation by activating the NF-κB signaling pathway, in a lipopolysaccharide (LPS)-induced model of AKI mice. For the present study, it was hypothesized that TLR2 inhibition could reduce inflammation and consequently prevent septic AKI. Therefore, the potential renal protective effects of ortho-vanillin (OV), an inhibitor of TLR2, were investigated in the present study in vitro and in vivo. In vitro treatment with OV on LPS-stimulated mouse podocyte cell line MPC5 did not affect TLR2 expression but interrupted the interaction between TLR2 and its downstream adaptor MyD88, resulting in the reduction of inflammatory cytokines IL-6 and TNF-α expression. In vivo OV treatment in an LPS-challenged mouse model effectively alleviated LPS-induced kidney injury as indicated by histology analysis and the significantly reduced blood urea nitrogen and serum creatinine levels. Additionally, inflammatory cytokines TNF-α, IL-6 and IL-1β expression were also significantly reduced in mice with OV treatment. Signaling pathway analysis further demonstrated that OV treatment did not affect the expression of TLR2 and p65 but suppressed p65 phosphorylation. Taken together, data from the present study demonstrated that OV was effective in protecting renal function against LPS-induced AKI through the inhibition of TLR2/NF-κB signaling and subsequent inflammatory cytokine production. These findings indicated that OV or targeting TLR2 signaling in general, represents a novel therapeutic approach for use in the prevention and treatment of AKI.

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“…The tubular epithelia produce TNF-α, IL-1, IL-16, IL-8, TGF-β, MCP-1, RANTES, ROS, and fractalkines (48). TNF-α is also produced by macrophages, lymphocytes, endothelial cells, epithelial cells, Schwann cells, mesangial cells, and podocytes in kidney (49). TNF-α is capable of inducing apoptosis and inflammation in renal epithelial cell (16) and can stimulate the production of reactive oxygen species (50).…”

Section: Role Of Cytokines In Pain Regulation During Akimentioning

confidence: 99%

Neuroimmune Mechanisms in Signaling of Pain During Acute Kidney Injury (AKI)

et al. 2020

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Acute kidney injury (AKI) is a significant global health concern. The primary causes of AKI include ischemia, sepsis and nephrotoxicity. The unraveled interface between nervous system and immune response with specific focus on pain pathways is generating a huge interest in reference to AKI. The nervous system though static executes functions by nerve fibers throughout the body. Neuronal peptides released by nerves effect the immune response to mediate the hemodynamic system critical to the functioning of kidney. Pain is the outcome of cellular cross talk between nervous and immune systems. The widespread release of neuropeptides, neurotransmitters and immune cells contribute to bidirectional neuroimmune cross talks for pain manifestation. Recently, we have reported pain pathway genes that may pave the way to better understand such processes during AKI. An auxiliary understanding of the functions and communications in these systems will lead to novel approaches in pain management and treatment through the pathological state, specifically during acute kidney injury.

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The role of podocyte damage in the etiology of ischemia-reperfusion acute kidney injury and post-injury fibrosis

Cited by 59 publications

References 30 publications

Sodium Oxalate-Induced Acute Kidney Injury Associated With Glomerular and Tubulointerstitial Damage in Rats

Sodium Oxalate-Induced Acute Kidney Injury Associated With Glomerular and Tubulointerstitial Damage in Rats

Treatment with toll‑like receptor 2 inhibitor ortho‑vanillin alleviates lipopolysaccharide‑induced acute kidney injury in mice

Neuroimmune Mechanisms in Signaling of Pain During Acute Kidney Injury (AKI)

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