Spatiotemporal Landscape of Kidney Tubular Responses to Glomerular Proteinuria

Journal of the American Society of Nephrology, Journal Year: 2024, Volume and Issue: unknown

Published: April 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.

Language: Английский

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Insights into the mechanisms of fibrosis and progressive kidney injury

Nature Reviews Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Language: 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, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 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

Language: Английский

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Animal models to study cognitive impairment of chronic kidney disease

AJP Renal Physiology, Journal Year: 2024, Volume and Issue: 326(6), P. F894 - F916

Published: April 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.

Language: Английский

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

Cell Reports, Journal Year: 2024, Volume and Issue: 43(8), P. 114569 - 114569

Published: July 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.

Language: 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, Journal Year: 2024, Volume and Issue: unknown, P. ard - 226336

Published: Oct. 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

Language: Английский

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Crosstalk between glomeruli and tubules

Nature Reviews Nephrology, Journal Year: 2024, Volume and Issue: 21(3), P. 189 - 199

Published: Dec. 6, 2024

Language: Английский

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Protein handling in kidney tubules

Nature Reviews Nephrology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Language: Английский

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SOX9: a key transcriptional regulator in organ fibrosis

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 5, 2025

The SOX9 gene locus is not only extensive but also intricate, and it could promote fibrosis in different organs or tissues, including cardiac fibrosis, liver kidney pulmonary as well other organ fibrosis. Many disorders are associated with the process of fibrosis; moreover, a common symptom chronic inflammatory diseases, characterized by accumulation excessive components extracellular matrix through signaling pathways. advanced stage fibrotic leads to dysfunction and, ultimately, death. In this review, we first give an overview original structure functions SOX9. Second, will discuss role various tissues. Third, describe reveal possibility antifibrotic treatment target. Finally, focus on application novel technologies for subsequent investigation

Language: Английский

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Bioprinting with Kidney Derived-Ecm for Extracellular Vesicle-Based Advanced Therapies

Published: Jan. 1, 2025

Language: Английский

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