Control of Directed Cell Migration after Tubular Cell Injury by Nucleotide Signaling DOI Open Access
Sabrina Gessler, Clara Guthmann,

Vera Schuler

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(14), P. 7870 - 7870

Published: July 17, 2022

Acute kidney injury (AKI) is a common complication of severe human diseases, resulting in increased morbidity and mortality as well unfavorable long-term outcomes. Although the mammalian endowed with an amazing capacity to recover from AKI, little progress has been made recent decades facilitate recovery AKI. To elucidate early repair mechanisms after we employed zebrafish pronephros model. Since damaged cells release large amounts ATP ATP-degradation products signal apoptosis or necrosis neighboring cells, examined how depletion purinergic adenosine receptors impacts directed cell migration that ensues immediately laser-induced tubular injury. We found adora1a, adora1b, adora2aa, adora2ab significantly affected process. Similar results were obtained p2ry2 receptor, which highly expressed during development. Released finally metabolized inosine by deaminase. Depletion deaminases ada ada2b interfered process; furthermore, combinations ada2b, ada2a displayed synergistic effects at low concentrations, supporting involvement signaling process Our findings suggest nucleotide-dependent controls immediate migratory responses

Language: Английский

Kidney fibrosis: from mechanisms to therapeutic medicines DOI Creative Commons

Rongshuang Huang,

Ping Fu, Liang Ma

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: March 17, 2023

Abstract Chronic kidney disease (CKD) is estimated to affect 10–14% of global population. Kidney fibrosis, characterized by excessive extracellular matrix deposition leading scarring, a hallmark manifestation in different progressive CKD; However, at present no antifibrotic therapies against CKD exist. fibrosis identified tubule atrophy, interstitial chronic inflammation and fibrogenesis, glomerulosclerosis, vascular rarefaction. Fibrotic niche, where organ initiates, complex interplay between injured parenchyma (like tubular cells) multiple non-parenchymal cell lineages (immune mesenchymal located spatially within scarring areas. Although the mechanisms are complicated due kinds cells involved, with help single-cell technology, many key questions have been explored, such as what kind renal tubules profibrotic, myofibroblasts originate, which immune how communicate each other. In addition, genetics epigenetics deeper that regulate fibrosis. And reversible nature epigenetic changes including DNA methylation, RNA interference, chromatin remodeling, gives an opportunity stop or reverse therapeutic strategies. More marketed (e.g., RAS blockage, SGLT2 inhibitors) developed delay progression recent years. Furthermore, better understanding also favored discover biomarkers fibrotic injury. review, we update advances mechanism summarize novel treatment for CKD.

Language: Английский

Citations

267
Integrative analysis of potential diagnostic markers and therapeutic targets for glomerulus-associated diabetic nephropathy based on cellular senescence DOI Creative Commons
Donglin Sun,

Shuqi Wei,

Dandan Wang

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 8, 2024

Introduction Diabetic nephropathy (DN), distinguished by detrimental changes in the renal glomeruli, is regarded as leading cause of death from end-stage disease among diabetics. Cellular senescence plays a paramount role, profoundly affecting onset and progression chronic kidney (CKD) acute injuries. This study was designed to delve deeply into pathological mechanisms between glomerulus-associated DN cellular senescence. Methods Glomerulus-associated datasets senescence-related genes were acquired Gene Expression Omnibus (GEO) CellAge database respectively. By integrating bioinformatics machine learning methodologies including LASSO regression analysis Random Forest, we screened out four signature genes. The receiver operating characteristic (ROC) curve performed evaluate diagnostic performance selected Rigorous experimental validations subsequently conducted mouse model corroborate identification three genes, namely LOX, FOXD1 GJA1. Molecular docking with chlorogenic acids (CGA) further established not only validate GJA1 markers but also reveal their potential therapeutic effects. Results discussion In conclusion, our findings pinpointed on basis These could predict an increased risk present promising targets, potentially ushering innovative treatments for elderly population.

Language: Английский

Citations

20
Chronic kidney disease and NLRP3 inflammasome: Pathogenesis, development and targeted therapeutic strategies DOI Creative Commons
Gengzhen Huang, Yaodan Zhang, Yingying Zhang

et al.

Biochemistry and Biophysics Reports, Journal Year: 2022, Volume and Issue: 33, P. 101417 - 101417

Published: Dec. 26, 2022

Chronic kidney disease (CKD) is a global health concern and public priority. The condition often involves inflammation due to the accumulation of toxins reduced clearance inflammatory cytokines, leading gradual loss function. Because tremendous burden CKD, finding effective treatment strategies against crucial. Substantial evidence suggests an association between inflammasome. As well-known multiprotein signaling complex, NLR family pyrin domain containing 3 (NLRP3) inflammasome plays important role in inducing renal fibrosis. Small molecule inhibitors targeting NLRP3 are potential agents for CKD.The activation amplifies response, promoting pyroptotic cell death. Thus, it may contribute onset progression but mechanism behind CKD remains obscure.In this review, we summarized recent findings on new

Language: Английский

Citations

31
STING deficiency alleviates ferroptosis through FPN1 stabilization in diabetic kidney disease DOI

Qin‐xiao Zhao,

Sen‐bo Yan,

Fen Wang

et al.

Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 222, P. 116102 - 116102

Published: Feb. 28, 2024

Language: Английский

Citations

8
Kidney function mediates the association of per- and poly-fluoroalkyl substances (PFAS) and heavy metals with hepatic fibrosis risk DOI
Zhengqi Wei,

Jincheng Liu,

Na Wang

et al.

Environmental Research, Journal Year: 2024, Volume and Issue: unknown, P. 120092 - 120092

Published: Sept. 1, 2024

Language: Английский

Citations

6
Renal tubular epithelial cell quality control mechanisms as therapeutic targets in renal fibrosis DOI Creative Commons
Yini Bao, Qiyuan Shan, Keda Lu

et al.

Journal of Pharmaceutical Analysis, Journal Year: 2024, Volume and Issue: 14(8), P. 100933 - 100933

Published: Jan. 4, 2024

Renal fibrosis is a devastating consequence of progressive chronic kidney disease, representing major public health challenge worldwide. The underlying mechanisms in the pathogenesis renal remain unclear, and effective treatments are still lacking. tubular epithelial cells (RTECs) maintain function, their dysfunction has emerged as critical contributor to fibrosis. Cellular quality control comprises several components, including telomere homeostasis, ubiquitin-proteasome system, autophagy, mitochondrial homeostasis (mitophagy metabolism), endoplasmic reticulum (unfolded protein response), lysosomes. Failures cellular RTECs, deoxyribonucleic acid (DNA), protein, organelle damage, exert profibrotic functions by leading senescence, defective stress, lysosomal dysfunction, apoptosis, fibroblast activation, immune cell recruitment. In this review, we summarize recent advances understanding role components intercellular crosstalk networks within context

Language: Английский

Citations

5
Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry DOI Creative Commons
Fabian Bock, Xinyu Dong, Shensen Li

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(6)

Published: Feb. 7, 2024

Prolonged obstruction of the ureter, which leads to injury kidney collecting ducts, results in permanent structural damage, while early reversal allows for repair. Cell structure is defined by actin cytoskeleton, dynamically organized small Rho guanosine triphosphatases (GTPases). In this study, we identified GTPase, Rac1, as a driver postobstructive duct After relief ureteric obstruction, Rac1 promoted cytoskeletal reconstitution, was required maintain normal mitotic morphology allowing successful cell division. Mechanistically, restricted excessive actomyosin activity that stabilized negative entry kinase Wee1. This mechanism ensured mechanical G 2 -M checkpoint stability and prevented premature entry. The repair defects following could be rescued direct myosin inhibition. Thus, Rac1-dependent control cytoskeleton integrates with cycle mediate tubular preventing dysmorphic cells from entering

Language: Английский

Citations

5
Current kidney function parameters overestimate kidney tissue repair in reversible experimental kidney disease DOI
Barbara M. Klinkhammer,

Simone Buchtler,

Sonja Djudjaj

et al.

Kidney International, Journal Year: 2022, Volume and Issue: 102(2), P. 307 - 320

Published: April 26, 2022

Language: Английский

Citations

22
Ankrd1 as a potential biomarker for the transition from acute kidney injury to chronic kidney disease DOI Creative Commons

Hailin Li,

Lemei Hu,

Changqing Zheng

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 7, 2025

Ischemia-reperfusion injury (IRI) is one of the leading causes acute kidney (AKI), predisposing patients to chronic disease (CKD) due maladaptive renal repair. Nevertheless, molecular mechanisms and biomarkers that cause repair remain unclear. In this study, we used single-nucleus RNA sequencing data from GEO database (GSE139107) identify markers during transition AKI CKD caused by IRI. Analysis intercellular crosstalk, trajectory machine learning algorithms revealed hub cell clusters genes. Proximal tubule (PT) cells, especially a new cluster (New PT2), significantly interacted with fibroblasts transition. The expression levels genes were validated using bulk RNA-seq (GSE98622) further confirmed through RT-qPCR immunohistochemical analysis in ischemia-reperfusion (uIRI) mice. Ankrd1, gene New PT2, showed sustained upregulation proximal AKI. Compared sham-operated group, Ankrd1 mice increased at 0.5 days post-reperfusion, peaked day 1, remained elevated up 60 days. This study indicated was positively associated progression may potentially serve as valuable biomarker for transitional process.

Language: Английский

Citations

0
Tubular-specific expression of HIV protein Vpr leads to severe tubulointerstitial damage accompanied by progressive fibrosis and cystic development DOI Creative Commons
Yuqiang Chen, Chen Ya, Jia Fu

et al.

Kidney International, Journal Year: 2022, Volume and Issue: 103(3), P. 529 - 543

Published: Dec. 22, 2022

Language: Английский

Citations

18