Spatiotemporal Landscape of Kidney Tubular Responses to Glomerular Proteinuria

Journal of the American Society of Nephrology, Год журнала: 2024, Номер unknown

Опубликована: Апрель 23, 2024

Key Points Glomerular proteinuria induces large-scale changes in gene expression along the nephron. Increased protein uptake proximal tubule results axial remodeling and injury. delivery to distal causes dedifferentiation of epithelium. Background Large increases glomerular filtration induce major body homeostasis are associated with a higher risk kidney functional decline cardiovascular disease. We investigated how elevated exposure modifies landscape tubular function entire nephron, understand cellular that mediate these important clinical phenomena. Methods conducted single-nucleus RNA sequencing, intravital imaging, antibody staining spatially map transport processes mouse tubule. then delineated were altered transgenic model inducible (POD-ATTAC) at 7 28 days. Results activated pleiotropic all nephron sections. Extension from early (S1) later (S2) parts initially triggered dramatic expansion hybrid S1/2 population, followed by injury failed repair, cumulative effect loss canonical S2 functions. Proteinuria also induced acute S3. Meanwhile, overflow luminal proteins caused transcriptional convergence between specialized regions generalized dedifferentiation. Conclusions modulated cell signaling epithelia distinct patterns segment-specific manner.

Язык: Английский

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Cross-talk of renal cells through WNT signal transduction in the development of fibrotic kidneys

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 12

Опубликована: Фев. 12, 2025

Chronic kidney disease (CKD) is a progressive condition that can lead to chronic renal failure (CRF), affecting 8%–16% of adults globally and imposing significant burden on healthcare systems. Renal fibrosis key pathological hallmark CKD progression linked poor prognosis. Multiple signaling pathways, including WNT/β-catenin.Aberrant activation WNT/β-catenin implicated in fibrosis. The roles macrophages fibroblasts are pivotal

Язык: Английский

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Insights into the mechanisms of fibrosis and progressive kidney injury

Nature Reviews Nephrology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 3, 2025

Язык: Английский

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Derepression of transposable elements enhances interferon beta signaling and stem/progenitor cell activity after proton irradiation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 15, 2024

Abstract Radiotherapy is a mainstay in cancer treatment, aiming to maximize DNA damage tumors while minimizing harm surrounding healthy tissues. However, the collateral normal tissues, especially stem/progenitor cells essential for tissue regeneration and organ function, remains significant challenge. Here, we investigate molecular responses photon proton irradiation, two key modalities head neck using organoids. Multiomics analysis reveals stronger double-stranded RNA (dsRNA)-induced type I interferon (IFN-I) response following driven by loss of heterochromatin regulators derepression transposable elements (TEs). This response, mediated cytoplasmic sensor RIG-I, enhances inflammatory signaling initiated canonical dsDNA sensors cGAS ZBP1. Genetic pharmacological modulation IFN-I vitro vivo demonstrates its critical role enhancing cell activity post-irradiation. Our findings reveal pro-regenerative TE derepression-mediated suggesting this pathway as promising therapeutic target mitigate radiation-induced side effects. Teaser Transposable element-mediated after irradiation.

Язык: Английский

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Animal models to study cognitive impairment of chronic kidney disease

AJP Renal Physiology, Год журнала: 2024, Номер 326(6), С. F894 - F916

Опубликована: Апрель 18, 2024

Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD), and its prevalence increases progressive loss of function. MCI characterized by a decline performance greater than expected for an individual age education level but minimal instrumental activities daily living. Deterioration can affect one or several domains (attention, memory, executive functions, language, perceptual motor social cognition). Given the increasing disease, more CKD will also develop causing enormous burden these individuals, their relatives, society. However, underlying pathomechanisms are poorly understood, current therapies mostly aim at supporting patients lives. This illustrates urgent need to elucidate pathogenesis potential therapeutic targets test novel appropriate preclinical models. Here, we outline necessary criteria experimental modeling disorders CKD. We discuss use mice, rats, zebrafish as model systems present valuable techniques through which function be assessed this setting. Our objective enable researchers overcome hurdles accelerate research aimed improving therapy MCI.

Язык: Английский

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IL-4-induced SOX9 confers lineage plasticity to aged adult lung stem cells

Cell Reports, Год журнала: 2024, Номер 43(8), С. 114569 - 114569

Опубликована: Июль 31, 2024

Wound healing in response to acute injury is mediated by the coordinated and transient activation of parenchymal, stromal, immune cells that resolves homeostasis. Environmental, genetic, epigenetic factors associated with inflammation aging can lead persistent microenvironment fibrosis. Here, we identify opposing roles interleukin-4 (IL-4) cytokine signaling interstitial macrophages type II alveolar epithelial (ATIIs). We show IL4Ra promotes regeneration epithelium after bleomycin-induced lung injury. Using organoids mouse models, IL-4 directly acts on a subset ATIIs induce expression transcription factor SOX9 reprograms them toward progenitor-like state both airway lineage potential. In contexts injury, this leads aberrant cell differentiation bronchiolization, consistent cellular histological changes observed disease.

Язык: Английский

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Imaging mass cytometry-based characterisation of fibroblast subsets and their cellular niches in systemic sclerosis

Annals of the Rheumatic Diseases, Год журнала: 2024, Номер unknown, С. ard - 226336

Опубликована: Окт. 23, 2024

Objectives Transcriptomic data demonstrated that fibroblasts are heterogeneous with functionally diverse subpopulations. Although key effector cells of fibrotic diseases such as systemic sclerosis (SSc), they have not yet been characterised spatially at the cellular level. Here, we aimed to investigate fibroblast subpopulations using imaging mass cytometry (IMC) a proteomic-based, resolved omics approach. Methods We applied IMC deconvolute heterogeneity 49 969 including 6501 single-cell level, analyse their spatial distribution and characterise niches in skin sections patients SSc controls situ. Results identified 13 different control skin, proportion increases five (myofibroblasts, FAP high , S1PR + Thy1 ;ADAM12 ;PU.1 ADAM12 ;GLI1 fibroblasts) decreases three (TFAM PI16 ;FAP low fibroblasts). Several enrichment altered interactions SSc. The -fibroblast positively correlated more extensive fibrosis, whereas numbers – -fibroblasts were associated milder fibrosis. frequency aberrant interaction between also extent fibrosis Conclusion Using IMC, profound changes composition localisation majority skin. These findings may provide rationale for specific targeting deregulated Quantification offer potential patient stratification according severity

Язык: Английский

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Crosstalk between glomeruli and tubules

Nature Reviews Nephrology, Год журнала: 2024, Номер 21(3), С. 189 - 199

Опубликована: Дек. 6, 2024

Язык: Английский

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Combined lineage tracing and scRNA‐seq reveal the activation of Sox9⁺ cells in renal regeneration with PGE₂ treatment

Cell Proliferation, Год журнала: 2024, Номер 57(11)

Опубликована: Май 27, 2024

Uncovering mechanisms of endogenous regeneration and repair through resident stem cell activation will allow us to develop specific therapies for injuries diseases by targeting lineages. Sox9

Язык: Английский

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Protein handling in kidney tubules

Nature Reviews Nephrology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 6, 2025

Язык: Английский

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