scholarly journals WNT1-inducible-signaling pathway protein 1 regulates kidney inflammation through the NF-κB pathway

2021 ◽  
Author(s):  
Bo Wang ◽  
Chenguang Ding ◽  
Xiaoming Ding ◽  
Greg H Tesch ◽  
Jin Zheng ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Regulatory Function ◽  
Pathological Feature ◽  
Novel Therapy ◽  
Kidney Fibrosis ◽  
Ureter Obstruction ◽  
Function Impairment ◽  
Pharmacological Blockade

Inflammation is a pathological feature of kidney injury and its progression correlates with the development of kidney fibrosis which can lead to kidney function impairment. This project investigated the regulatory function of WNT1-inducible-signaling pathway protein 1 (WISP1) in kidney inflammation. Administration of recombinant WISP1 protein to healthy mice induced kidney inflammation (macrophage accrual and production of TNFα, CCL2 and IL-6), which could be prevented by inhibition of NF-κB. Furthermore, inhibition of WISP1, by gene knockdown or neutralising antibody, could inhibit cultured macrophages producing inflammatory cytokines following stimulation with lipopolysaccharides (LPS) and kidney fibroblasts proliferating in response to TNFα, which both involved NF-κB signalling.  Kidney expression of WISP1 was found to be increased in mouse models of progressive kidney inflammation- unilateral ureter obstruction (UUO) and streptozotocin-induced diabetic nephropathy. Treatment of UUO mice with WISP1 antibody reduced the kidney inflammation in these mice. Therefore, pharmacological blockade of WISP1 exhibits potential as a novel therapy for inhibiting inflammation in kidney disease.

scholarly journals Targeting Ferroptosis Attenuates Interstitial Inflammation and Kidney Fibrosis

2021 ◽  
pp. 1-15
Author(s):  
Lu Zhou ◽  
Xian Xue ◽  
Qing Hou ◽  
Chunsun Dai
Keyword(s):  
Mouse Models ◽  
Ischemia Reperfusion Injury ◽  
Interstitial Fibrosis ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Epithelial Cell ◽  
Kidney Fibrosis ◽  
Ureter Obstruction ◽  
Regulated Necrosis ◽  
Dependent Form

<b><i>Background:</i></b> Ferroptosis, an iron-dependent form of regulated necrosis mediated by lipid peroxidation, predominantly polyunsaturated fatty acids, is involved in postischemic and toxic kidney injury. However, the role and mechanisms for tubular epithelial cell (TEC) ferroptosis in kidney fibrosis remain largely unknown. <b><i>Objectives:</i></b> The aim of the study was to decipher the role and mechanisms for TEC ferroptosis in kidney fibrosis. <b><i>Methods:</i></b> Mouse models with unilateral ureter obstruction (UUO) or ischemia/reperfusion injury (IRI) were generated. <b><i>Results:</i></b> We found that TEC ferroptosis exhibited as reduced glutathione peroxidase 4 (GPX4) expression and increased 4-hydroxynonenal abundance was appeared in kidneys from chronic kidney disease (CKD) patients and mouse models with UUO or IRI. Inhibition of ferroptosis could largely mitigate kidney injury, interstitial fibrosis, and inflammatory cell accumulation in mice after UUO or IRI. Additionally, treatment of TECs with (1S,3R)-RSL-3, an inhibitor of GPX4, could enhance cell ferroptosis and recruit macrophages. Furthermore, inhibiting TEC ferroptosis reduced monocyte chemotactic protein 1 (MCP-1) secretion and macrophage chemotaxis. <b><i>Conclusions:</i></b> This study uncovers that TEC ferroptosis may promote interstitial fibrosis and inflammation, and targeting ferroptosis may shine a light on protecting against kidney fibrosis in patients with CKDs.

Novel Chalcone BDD-39 Mitigated Diabetic Nephropathy through the Activation of Nrf2/ARE Signaling

2021 ◽  
Vol 14 ◽  
Author(s):  
Temitope Adelusi ◽  
Xizhi Li ◽  
Liu Xu ◽  
Lei Du ◽  
Meng Hao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Nuclear Translocation ◽  
Mesangial Cells ◽  
Intraperitoneal Administration ◽  
Mrna Levels ◽  
Glomerular Mesangial Cells ◽  
Kidney Fibrosis

Background: In this study, we investigated the Nrf2/ARE signaling pathway activating capacity of Biphenyl Diester Derivative-39 (BDD-39) in diabetic nephropathy in order to elucidate the mechanism surrounding its antidiabetic potential. Objectives: Protein expressions of Nrf2, HO-1, NQO-1 and biomarkers of kidney fibrosis were executed after which mRNA levels of Nrf2, HO-1 and NQO-1 were estimated after creating the models following BBD-39 treatment. Methods: Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with BDD-39 (15, 45mg· kg-1· d-1, ig) or a positive control drug resveratrol (45mg· kg-1·d-1, ig) for 8 weeks. Staining techniques were used to investigate collagen deposition in the glomerulus of the renal cortex and also to investigate the expression and localization of Nrf2 and extracellular matrix (ECM) proteins (collagen IV and laminin) in vitro and in vivo. Furthermore, we studied the mechanism of action of BDD-39 using RNA-mediated Nrf2 silencing technique in mouse SV40 glomerular mesangial cells (SV40 GM cells). Results : We found that BDD-39 activates Nrf2/ARE signaling pathway, promotes Nrf2 nuclear translocation (Nrf2nuc/Nrf2cyt) and modulate prominent biomarkers of kidney fibrosis at the protein level. However, BDD-39 could not activate Nrf2/ARE signaling in RNA-mediated Nrf2-silenced HG-cultured SV40 GM cells. Conclusion: Taken together, this study demonstrates for the first time that BDD-39 ameliorates experimental DN through attenuation of renal fibrosis progression and modulation of Nrf2/ARE signaling pathway.

1138-P: Empagliflozin Ameliorates Kidney Injury in Diabetic Nephropathy via SIRT1 and TXNIP

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1138-P
Author(s):  
RIYING LIANG ◽  
MEIJUN WANG ◽  
FEN XU ◽  
MENGYIN CAI
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Injury

Sitagliptin relieves diabetic nephropathy fibrosis via the MAPK/ERK signaling pathway

2020 ◽  
Vol 45 (3) ◽  
Author(s):  
Shufeng Cheng ◽  
Liang Li ◽  
Chunquan Song ◽  
Huijing Jin ◽  
Shouguo Ma ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Erk Signaling

scholarly journals PP2Acα promotes macrophage accumulation and activation to exacerbate tubular cell death and kidney fibrosis through activating Rap1 and TNFα production

2021 ◽  
Author(s):  
Yan Liang ◽  
Xiaoli Sun ◽  
Mingjie Wang ◽  
Qingmiao Lu ◽  
Mengru Gu ◽  
...  
Keyword(s):  
Cell Death ◽  
Tubular Cell ◽  
Kidney Fibrosis ◽  
Tubular Cells ◽  
Ureter Obstruction ◽  
Underlying Mechanisms ◽  
Factor Α ◽  
Rap1 Activation ◽  
Necrosis Factor ◽  
Macrophage Accumulation

AbstractMacrophage accumulation and activation play an essential role in kidney fibrosis; however, the underlying mechanisms remain to be explored. By analyzing the kidney tissues from patients and animal models with kidney fibrosis, we found a large induction of PP2Acα in macrophages. We then generated a mouse model with inducible macrophage ablation of PP2Acα. The knockouts developed less renal fibrosis, macrophage accumulation, or tubular cell death after unilateral ureter obstruction or ischemic reperfusion injury compared to control littermates. In cultured macrophages, PP2Acα deficiency resulted in decreased cell motility by inhibiting Rap1 activity. Moreover, co-culture of PP2Acα−/− macrophages with tubular cells resulted in less tubular cell death attributed to downregulated Stat6-mediated tumor necrosis factor α (TNFα) production in macrophages. Together, this study demonstrates that PP2Acα promotes macrophage accumulation and activation, hence accelerates tubular cell death and kidney fibrosis through regulating Rap1 activation and TNFα production.

LncRNA TUG1 ameliorates diabetic nephropathy via inhibition of PU.1/RTN1 signaling pathway

2021 ◽  
Author(s):  
Dongdong Meng ◽  
Lina Wu ◽  
Zhifu Li ◽  
Xiaojun Ma ◽  
Shuiying Zhao ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Lncrna Tug1
Sign in / Sign up

Export Citation Format

Share Document