KIM-1 augments hypoxia-induced tubulointerstitial inflammation through uptake of small extracellular vesicles by tubular epithelial cells

Chen, Jun; Tang, Tao-Tao; Cao, Jun; Li, Zuo‐Lin; Zhong, Xin; Wen, Yi; Shen, Anran; Liu, Bi‐Cheng; Lv, Lin‐Li

doi:10.1016/j.ymthe.2022.08.013

Cited by 19 publications

(16 citation statements)

References 52 publications

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“…The immunomodulatory medication Thalidomide attenuated macrophage infiltration and reduced kidney interstitial fibrosis [56]. KIM-1 expressed by injured tubules mediates small extracellular vesicle uptake by recognizing phosphatidylserine, a ligand of KIM-1, amplificating tubule inflammation induced by hypoxia [57]. Specific deletion of TGF-βRII in macrophages prevents from interstitial fibrosis following renal ischemia-reperfusion injury (IRI) [58].…”

Section: Inflammationmentioning

confidence: 99%

Hypoxia-Driven Responses in Chronic Kidney Disease

Miguel

Rojo

2023

Oxygen

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Chronic kidney disease (CKD) affects 10% of the population. Fibrosis is the hallmark of CKD, which is marked by the deposit of extracellular matrix (ECM). This response is the final outcome of an unbalanced reaction to inflammation and wound healing and can be induced by a variety of insults, including hypoxia. Vascular damage results in an impaired tissue oxygen supply, inducing immune cell infiltration, tubule injury and the activation of ECM-secreting myofibroblasts. In turn, tubulointerstitial fibrosis development worsens oxygen diffusion. Hypoxia-inducible factor (HIF) is the primary transcriptional regulator of hypoxia-associated responses, such as oxidative stress and metabolic reprogramming, triggering a proinflammatory and profibrotic landscape. In this review, we discuss hypoxia-driven reprogramming in CKD as well as potential therapeutic approaches to target chronic hypoxia.

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Section: Inflammationmentioning

confidence: 99%

Hypoxia-Driven Responses in Chronic Kidney Disease

Miguel

Rojo

2023

Oxygen

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“…There was a complex mutual regulation between hypoxia and inflammation, [ 51 , 52 ] and Chen et al validated that tubular epithelial cells exposed to hypoxia would incite tubulointerstitial inflammation. [ 53 ] In all, these indicated that TwHF might activate PI3K-Akt signaling pathway as well as TNF signaling pathway to progress renal inflammation, mediate hypoxia via HIF-1 signaling pathway to accelerate inflammatory processes. In addition, AMPK signaling pathway was confirmed to be involved in podocyte injury [ 54 ] that provided a probable position of TwHF induced KI, and FoxOs involved in diverse intracellular signaling pathways with critical roles in various physiological as well as pathological conditions [ 55 ] while the relationship between FoxOs with KI needed to further research.…”

Section: Discussionmentioning

confidence: 99%

Tripterygium wilfordii Hook.f induced kidney injury through mediating inflammation via PI3K-Akt/HIF-1/TNF signaling pathway: A study of network toxicology and molecular docking

Yang,

Wang,

et al. 2024

Medicine

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We intend to explore potential mechanisms of Tripterygium wilfordii Hook.f (TwHF) induced kidney injury (KI) using the methods of network toxicology and molecular docking. We determined TwHF potential compounds with its targets and KI targets, obtained the TwHF induced KI targets after intersecting targets of TwHF and KI. Then we conducted protein-protein interaction (PPI) network, gene expression analysis, gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis to explore the mechanism of TwHF-induced KI. Finally we conducted molecular docking to verify the core toxic compounds and the targets. We obtained 12 TwHF toxic compounds and 62 TwHF-induced KI targets. PPI network, gene expression analysis and GO function enrichment analysis unveiled the key biological process and suggested the mechanism of TwHF-induced KI might be associated with inflammation, immune response, hypoxia as well as oxidative stress. KEGG pathway enrichment analysis indicated PI3K-Akt signaling pathway, HIF-1 signaling pathway and TNF signaling pathway were key signaling pathways of TwHF induced KI. Molecular docking showed that the binding energy of core targets and toxic compounds was all less than −6.5 kcal/mol that verified the screening ability of network pharmacology and provided evidence for modifying TwHF toxic compounds structure. Through the study, we unveiled the mechanism of TwHF induce KI that TwHF might activate PI3K-Akt signaling pathway as well as TNF signaling pathway to progress renal inflammation, mediate hypoxia via HIF-1 signaling pathway to accelerate inflammatory processes, and also provided a theoretical basis for modifying TwHF toxic compounds structure as well as supported the follow-up research.

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“…KIM1 has been proposed as a novel urine biomarker for CKD ( Han et al, 2002 ; Khreba et al, 2019 ). Recently, Jun et al, showed that KIM1 is necessary for EVs uptake by tubular epithelial cells ( Chen et al, 2023 ).…”

Section: Early Detection Biomarkersmentioning

confidence: 99%

Comprehensive strategy for identifying extracellular vesicle surface proteins as biomarkers for chronic kidney disease

Garcia,

Gonzalez-King,

Mellergaard

et al. 2024

Front. Physiol.

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Chronic kidney disease (CKD) poses a significant health burden worldwide. Especially, obesity-induced chronic kidney disease (OCKD) is associated with a lack of accuracy in disease diagnostic methods. The identification of reliable biomarkers for the early diagnosis and monitoring of CKD and OCKD is crucial for improving patient outcomes. Extracellular vesicles (EVs) have emerged as potential biomarkers in the context of CKD. In this review, we focused on the role of EVs as potential biomarkers in CKD and OCKD and developed a comprehensive list of EV membrane proteins that could aid in the diagnosis and monitoring of the disease. To assemble our list, we employed a multi-step strategy. Initially, we conducted a thorough review of the literature on EV protein biomarkers in kidney diseases. Additionally, we explored papers investigating circulating proteins as biomarkers in kidney diseases. To further refine our list, we utilized the EV database Vesiclepedia.org to evaluate the qualifications of each identified protein. Furthermore, we consulted the Human Protein Atlas to assess the localization of these candidates, with a particular focus on membrane proteins. By integrating the information from the reviewed literature, Vesiclepedia.org, and the Human Protein Atlas, we compiled a comprehensive list of potential EV membrane protein biomarkers for CKD and OCKD. Overall, our review underscores the potential of EVs as biomarkers in the field of CKD research, providing a foundation for future studies aimed at improving CKD and OCKD diagnosis and treatment.

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KIM-1 augments hypoxia-induced tubulointerstitial inflammation through uptake of small extracellular vesicles by tubular epithelial cells

Cited by 19 publications

References 52 publications

Hypoxia-Driven Responses in Chronic Kidney Disease

Hypoxia-Driven Responses in Chronic Kidney Disease

Tripterygium wilfordii Hook.f induced kidney injury through mediating inflammation via PI3K-Akt/HIF-1/TNF signaling pathway: A study of network toxicology and molecular docking

Comprehensive strategy for identifying extracellular vesicle surface proteins as biomarkers for chronic kidney disease

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