Retinoic acid receptor α activity in proximal tubules prevents kidney injury and fibrosis DOI
Krysta M. DiKun, Xiao‐Han Tang,

Leiping Fu

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(7)

Опубликована: Фев. 8, 2024

Chronic kidney disease (CKD) is characterized by a gradual loss of function and affects ~13.4% the global population. Progressive tubulointerstitial fibrosis, driven in part proximal tubule (PT) damage, hallmark late stages CKD contributes to development failure, for which there are limited treatment options. Normal requires signaling vitamin A (retinol), metabolized retinoic acid (RA), an endogenous agonist RA receptors (RARα, β, γ). RARα levels decreased mouse model diabetic nephropathy restored with administration; additionally, reduced fibrosis. We developed spatiotemporal (tamoxifen-inducible) deletion PT cells adult mice causes mitochondrial dysfunction, massive injury, apoptosis without use additional nephrotoxic substances. Long-term effects (3 4.5 mo) include increased secretion transforming growth factor β1, inflammation, interstitial function, all major features human CKD. Therefore, RARα’s actions PTs crucial homeostasis, injury key phenotype.

Язык: Английский

Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease DOI
Alla Mitrofanova, Sandra Merscher, Alessia Fornoni

и другие.

Nature Reviews Nephrology, Год журнала: 2023, Номер 19(10), С. 629 - 645

Опубликована: Июль 27, 2023

Язык: Английский

Процитировано

126
Transcriptomic, epigenomic, and spatial metabolomic cell profiling redefines regional human kidney anatomy DOI Creative Commons
Haikuo Li, Dian Li, Nicolas Ledru

и другие.

Cell Metabolism, Год журнала: 2024, Номер 36(5), С. 1105 - 1125.e10

Опубликована: Март 20, 2024

A large-scale multimodal atlas that includes major kidney regions is lacking. Here, we employed simultaneous high-throughput single-cell ATAC/RNA sequencing (SHARE-seq) and spatially resolved metabolomics to profile 54 human samples from distinct anatomical regions. We generated transcriptomes of 446,267 cells chromatin accessibility profiles 401,875 developed a package analyze 408,218 metabolomes. find the same cell type, including thin limb, thick ascending limb loop Henle principal cells, display transcriptomic, accessibility, metabolomic signatures, depending on anatomic location. Surveying metabolism-associated gene revealed non-overlapping metabolic signatures between nephron segments dysregulated lipid metabolism in diseased proximal tubule (PT) cells. Integrating omics with clinical data identified PLEKHA1 as disease marker, its vitro knockdown increased expression PT differentiation, suggesting possible pathogenic roles. This study highlights previously underrepresented cellular heterogeneity underlying anatomy.

Язык: Английский

Процитировано

33
Predicting proximal tubule failed repair drivers through regularized regression analysis of single cell multiomic sequencing DOI Creative Commons
Nicolas Ledru, Parker C. Wilson, Yoshiharu Muto

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 12, 2024

Abstract Renal proximal tubule epithelial cells have considerable intrinsic repair capacity following injury. However, a fraction of injured fails to undergo normal and assumes proinflammatory profibrotic phenotype that may promote fibrosis chronic kidney disease. The healthy failed change is marked by cell state-specific transcriptomic epigenomic changes. Single nucleus joint RNA- ATAC-seq sequencing offers an opportunity study the gene regulatory networks underpinning these changes in order identify key drivers. We develop regularized regression approach construct genome-wide parametric using multiomic datasets. generate single dataset from seven adult human samples apply our method drivers injury response associated with demonstrate highly effective tool for predicting cis- trans- elements transition use it NFAT5 as driver maladaptive state.

Язык: Английский

Процитировано

27
The key role of altered tubule cell lipid metabolism in kidney disease development DOI Creative Commons
Lauren E. Lee, Tomohito Doke, Dhanunjay Mukhi

и другие.

Kidney International, Год журнала: 2024, Номер 106(1), С. 24 - 34

Опубликована: Апрель 16, 2024

Kidney epithelial cells have very high energy requirements, which are largely met by fatty acid oxidation. Complex changes in lipid metabolism observed patients with kidney disease. Defects oxidation and increased uptake, especially the context of hyperlipidemia proteinuria, contribute to this excess build-up exacerbate disease development. Recent studies also highlighted role de novo lipogenesis fibrosis. The defect causes starvation. Increased synthesis, lower can cause toxic build-up, reactive oxygen species generation, mitochondrial damage. A better understanding these metabolic processes may open new treatment avenues for diseases targeting metabolism.

Язык: Английский

Процитировано

24
Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease DOI
Verónica Miguel, Isaac Shaw, Rafael Kramann

и другие.

Nature Reviews Nephrology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 17, 2024

Язык: Английский

Процитировано

19
Fisetin ameliorates fibrotic kidney disease in mice via inhibiting ACSL4-mediated tubular ferroptosis DOI
Bo Wang, Lina Yang,

Letian Yang

и другие.

Acta Pharmacologica Sinica, Год журнала: 2023, Номер 45(1), С. 150 - 165

Опубликована: Сен. 11, 2023

Язык: Английский

Процитировано

34
Mechanisms of kidney fibrosis and routes towards therapy DOI
N. Yamashita, Rafael Kramann

Trends in Endocrinology and Metabolism, Год журнала: 2023, Номер 35(1), С. 31 - 48

Опубликована: Сен. 28, 2023

Язык: Английский

Процитировано

34
Fibrosis in Pathology of Heart and Kidney: From Deep RNA-Sequencing to Novel Molecular Targets DOI Open Access
Felix Schreibing, Teresa M Anslinger, Rafael Kramann

и другие.

Circulation Research, Год журнала: 2023, Номер 132(8), С. 1013 - 1033

Опубликована: Апрель 13, 2023

Diseases of the heart and kidney, including failure chronic kidney disease, can dramatically impair life expectancy quality patients. The form a functional axis; therefore, impairment 1 organ will inevitably affect function other. Fibrosis represents common final pathway diseases both organs, regardless disease entity. Thus, inhibition fibrosis promising therapeutic approach to treat organs resolve impairment. However, despite growing knowledge in this field, exact pathomechanisms that drive remain elusive. RNA-sequencing approaches, particularly single-cell RNA-sequencing, have revolutionized investigation at molecular level facilitated discovery disease-associated cell types mechanisms. In review, we give brief overview over evolution techniques, summarize most recent insights into pathogenesis fibrosis, discuss how transcriptomic data be used, identify new drug targets develop novel strategies.

Язык: Английский

Процитировано

32
LIANA+: an all-in-one cell-cell communication framework DOI Creative Commons
Daniel Dimitrov, Philipp Schäfer, Elias Farr

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Авг. 21, 2023

Abstract The growing availability of single-cell and spatially-resolved transcriptomics has led to the rapidly popularity methods infer cell-cell communication. Many approaches have emerged, each capturing only a partial view complex landscape Here, we present LIANA+, scalable framework decode coordinated inter- intracellular signalling events from single- multi-condition datasets in both data. Beyond integrating extending established methodologies rich knowledge base, LIANA+ enables novel analyses using diverse molecular mediators, including those measured multi-omics Accessible as an open-source Python package at https://github.com/saezlab/liana-py , provides comprehensive set synergistic components study Figure

Язык: Английский

Процитировано

24
High resolution spatial profiling of kidney injury and repair using RNA hybridization-based in situ sequencing DOI Creative Commons
Hao Wu, Eryn E. Dixon, Qiao Xuanyuan

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Фев. 15, 2024

Abstract Emerging spatially resolved transcriptomics technologies allow for the measurement of gene expression in situ at cellular resolution. We apply direct RNA hybridization-based sequencing (dRNA HybISS, Cartana part 10xGenomics) to compare male and female healthy mouse kidneys kidney injury repair timecourse. A pre-selected panel 200 genes is used identify cell state dynamics patterns during repair. develop a new computational pipeline, CellScopes, rapid analysis, multi-omic integration visualization transcriptomic datasets. The resulting dataset allows us resolve 13 types within distinct niches, dynamic alterations over course cell-cell interactions between leukocytes parenchyma. At late timepoints after injury, C3+ are enriched near pro-inflammatory, failed-repair proximal tubule cells. Integration snRNA-seq from same samples also impute spatial localization not directly measured by dRNA HybISS.

Язык: Английский

Процитировано

16