Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice

2016 ◽  
Vol 38 ◽  
pp. 409-419 ◽  
Author(s):  
Xiaoying Xu ◽  
Linfeng Gou ◽  
Meng Zhou ◽  
Fusheng Yang ◽  
Yihan Zhao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Renal Cell ◽  
Inflammatory Responses ◽  
Kidney Injury

scholarly journals TNF Superfamily: A Growing Saga of Kidney Injury Modulators

2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Maria D. Sanchez-Niño ◽  
Alberto Benito-Martin ◽  
Sara Gonçalves ◽  
Ana B. Sanz ◽  
Alvaro C. Ucero ◽  
...  
Keyword(s):  
Cell Death ◽  
Renal Cell ◽  
Fas Ligand ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Therapeutic Targeting ◽  
Tubular Cells ◽  
Tnf Superfamily ◽  
Nf Kappab

Members of the TNF superfamily participate in kidney disease. Tumor necrosis factor (TNF) and Fas ligand regulate renal cell survival and inflammation, and therapeutic targeting improves the outcome of experimental renal injury. TNF-related apoptosis-inducing ligand (TRAIL and its potential decoy receptor osteoprotegerin are the two most upregulated death-related genes in human diabetic nephropathy. TRAIL activates NF-kappaB in tubular cells and promotes apoptosis in tubular cells and podocytes, especially in a high-glucose environment. By contrast, osteoprotegerin plays a protective role against TRAIL-induced apoptosis. Another family member, TNF-like weak inducer of apoptosis (TWEAK induces inflammation and tubular cell death or proliferation, depending on the microenvironment. While TNF only activates canonical NF-kappaB signaling, TWEAK promotes both canonical and noncanonical NF-kappaB activation in tubular cells, regulating different inflammatory responses. TWEAK promotes the secretion of MCP-1 and RANTES through NF-kappaB RelA-containing complexes and upregulates CCl21 and CCL19 expression through NF-kappaB inducing kinase (NIK-) dependent RelB/NF-kappaB2 complexes. In vivo TWEAK promotes postnephrectomy compensatory renal cell proliferation in a noninflammatory milieu. However, in the inflammatory milieu of acute kidney injury, TWEAK promotes tubular cell death and inflammation. Therapeutic targeting of TNF superfamily cytokines, including multipronged approaches targeting several cytokines should be further explored.

scholarly journals A Porthole over AKI: Cell Dynamics in Damage and Repair

Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 650-654
Author(s):  
Luca Bordoni ◽  
Donato Sardella ◽  
Ina Maria Schiessl
Keyword(s):  
Acute Kidney Injury ◽  
Renal Cell ◽  
Kidney Injury ◽  
Cell Types ◽  
Cell Interactions ◽  
Intravital Imaging ◽  
Cell Dynamics ◽  
Powerful Technique ◽  
Increased Risk ◽  
Cell Crosstalk

Acute kidney injury (AKI) is associated with an increased risk of CKD. Injury-induced multifaceted renal cell-to-cell crosstalk can either lead to successful self-repair or chronic fibrosis and inflammation. In this mini-review, we will discuss critical renal cell types acting as victims or executioners in AKI pathology and introduce intravital imaging as a powerful technique to further dissect these cell-to-cell interactions.

scholarly journals miR-34b-5p promotes renal cell inflammation and apoptosis by inhibiting aquaporin-2 in sepsis-induced acute kidney injury

Renal Failure ◽  
2021 ◽  
Vol 43 (1) ◽  
pp. 291-301
Author(s):  
Caifa Zheng ◽  
Dansen Wu ◽  
Songjing Shi ◽  
Liming Wang
Keyword(s):  
Acute Kidney Injury ◽  
Renal Cell ◽  
Kidney Injury ◽  
Aquaporin 2

scholarly journals DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yinwu Bao ◽  
Mengqiu Bai ◽  
Huanhuan Zhu ◽  
Yuan Yuan ◽  
Ying Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Injury ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Clinical Samples ◽  
Mice Model ◽  
Expression Levels ◽  
Ppar Signaling

AbstractDemethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

2021 ◽  
Vol 118 (37) ◽  
pp. e2104347118
Author(s):  
Ravi Shankar Keshari ◽  
Narcis Ioan Popescu ◽  
Robert Silasi ◽  
Girija Regmi ◽  
Cristina Lupu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Anemia ◽  
Complement Activation ◽  
Inflammatory Responses ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Multiple Organ ◽  
Immune Recognition ◽  
Gram Positive ◽  
Terminal Complement

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

Pathogenesis of Acute Kidney Injury

2019 ◽  
pp. 11-20
Author(s):  
David P. Basile ◽  
Babu J. Padanilam
Keyword(s):  
Acute Kidney Injury ◽  
Cell Death ◽  
Renal Function ◽  
Fatty Acid ◽  
Interstitial Fibrosis ◽  
Kidney Injury ◽  
Acid Oxidation ◽  
Clinical Disorder ◽  
Successful Recovery ◽  
Multiple Issues

Acute kidney injury represents a significant clinical disorder associated with a rapid loss of renal function following a variety of potential insults. This chapter reviews multiple issues related to the pathophysiology of AKI with an emphasis on studies from animal models. Early responses following kidney injury include impaired hemodynamic and bioenergetic responses. Reductions in renal ATP levels occur as a result of compromised fatty acid oxidation and impaired compensation by glycolysis. Sustained reductions in perfusion contribute to extension of AKI characterized by complex inflammatory and cellular injury responses, often leading to cell death. Concurrently, the kidney displays an elegant repair response, leading to successful recovery in most cases, characterized in part by epithelial cell growth, while maladaptive or incomplete recovery of tubules or capillaries can predispose the development of interstitial fibrosis and CKD progression.

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