The Kidney Precision Medicine Project and Single-Cell Biology of the Injured Proximal Tubule DOI
Danielle Janosevic, Thomas De Luca, Michael T. Eadon

и другие.

American Journal Of Pathology, Год журнала: 2024, Номер 195(1), С. 7 - 22

Опубликована: Сен. 26, 2024

Язык: Английский

Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities DOI Creative Commons
Dongxue Xu, Xiaoyu Zhang, Jingjing Pang

и другие.

Biomolecules, Год журнала: 2025, Номер 15(6), С. 794 - 794

Опубликована: Май 29, 2025

Acute kidney injury (AKI) causes damage to the renal epithelium, initiating a reparative process intended restore function. Although effective repair can result in complete recovery of function, this is frequently incomplete. In instances where unsuccessful, experiences maladaptive alterations that may progressively chronic disease (CKD), phenomenon referred as failed repair. This condition precipitated by hypotensive, septic, or toxic insults, which initiate series pathophysiological processes, including microcirculatory dysfunction, activation inflammatory responses, and death tubular epithelial cells. These events collectively compromise function trigger complex response. review provides comprehensive examination multifactorial mechanisms underlying initiation progression AKI, regenerative pathways facilitating structural severely damaged kidneys, critical transition from adaptive remodeling. Central are such epigenetic reprogramming, G2/M cell-cycle arrest, cellular senescence, mitochondrial metabolism cell death, drive CKD. mechanistic insights offer robust foundation for development targeted therapeutic strategies aimed at enhancing

Язык: Английский

Процитировано

0

Multi-omics profiling of mouse polycystic kidney disease progression at a single cell resolution DOI Creative Commons
Yoshiharu Muto, Yasuhiro Yoshimura, Hao Wu

и другие.

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

Опубликована: Июнь 1, 2024

Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary and causes significant morbidity, ultimately leading to end-stage disease. PKD pathogenesis characterized by complex dynamic alterations in multiple cell types during progression, hampering a deeper understanding of mechanism development therapeutic approaches. Here, we generate single nucleus multimodal atlas an orthologous mouse model at early, mid late timepoints, consisting 125,434 single-nucleus transcriptomic epigenetic multiomes. We catalogue differentially expressed genes activated regions each type characterizing cell-type-specific responses Pkd1 deletion. describe heterogeneous, atypical collecting duct cells as well proximal tubular that constitute cyst epithelia PKD. The transcriptional regulation lining marker GPRC5A conserved between human cystic epithelia, suggesting shared gene regulatory pathways. Our multiomic analysis provides foundation understand earliest changes molecular deregulation single-cell resolution.

Язык: Английский

Процитировано

2

Stepwise developmental mimicry generates proximal-biased kidney organoids DOI
Jack Schnell, Zhen Miao, MaryAnne Achieng

и другие.

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

Опубликована: Июль 2, 2024

The kidney maintains body fluid homeostasis by reabsorbing essential compounds and excreting waste. Proximal tubule cells, crucial for renal reabsorption of a range sugars, ions, amino acids, are highly susceptible to damage, leading pathologies necessitating dialysis transplants. While human pluripotent stem cell-derived organoids used modeling development, disease, injury, the formation proximal nephron cells in these 3D structures is incomplete. Here, we describe how drive development precursors following blueprint

Язык: Английский

Процитировано

2

Biology of the proximal tubule in body homeostasis and kidney disease DOI
Melanie P. Hoenig, Craig R. Brooks, Ewout J. Hoorn

и другие.

Nephrology Dialysis Transplantation, Год журнала: 2024, Номер unknown

Опубликована: Июль 25, 2024

The proximal tubule (PT) is known as the workhorse of kidney, both for range and magnitude functions that it performs. It not only responsible reabsorbing most solutes proteins filtered by glomeruli, but also secreting non-filtered substances including drugs uremic toxins. PT therefore plays a pivotal role in kidney physiology body homeostasis. Moreover, major site damage acute injury nephrotoxicity. In this review, we will provide an introduction to cell biology explore how adapted execution myriad different these can differ between males females. We then discuss regulates phosphate, glucose acid-base balance, consequences alterations function bone cardiovascular health. Finally, why vulnerable ischemic toxic insults, lead maladaptive repair, chronic damage, fibrosis. summary, demonstrate knowledge basic critical understanding disease phenotypes their associated systemic complications, developing new therapeutic strategies prevent these.

Язык: Английский

Процитировано

2

The Kidney Precision Medicine Project and Single-Cell Biology of the Injured Proximal Tubule DOI
Danielle Janosevic, Thomas De Luca, Michael T. Eadon

и другие.

American Journal Of Pathology, Год журнала: 2024, Номер 195(1), С. 7 - 22

Опубликована: Сен. 26, 2024

Язык: Английский

Процитировано

2