SOX9: a key transcriptional regulator in organ fibrosis

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Фев. 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

Язык: Английский

---

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

Опубликована: Янв. 1, 2025

Язык: Английский

---

Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury

Journal of Clinical Investigation, Год журнала: 2025, Номер 135(6)

Опубликована: Март 16, 2025

Acute kidney injury (AKI) encompasses pathophysiology ranging from glomerular hypofiltration to tubular cell and outflow obstruction. This Review will focus on the tubulointerstitial processes that underlie most cases of AKI. Tubular epithelial (TEC) can occur via distinct insults, including ischemia, nephrotoxins, sepsis, primary immune-mediated processes. Following these initial cells activate survival repair responses or they develop mitochondrial dysfunction metabolic reprogramming, cell-cycle arrest, programmed death. Developing evidence suggests fate individual survive proliferate undergo death senescence is frequently determined by a biphasic immune response with proinflammatory macrophage, neutrophil, lymphocyte infiltration exacerbating activating death, while alternatively activated macrophages specific subsets subsequently modulate inflammation promote repair. Functional recovery requires this reparative phase supports proteolytic degradation casts, proliferation surviving TECs, restoration TEC differentiation. Incomplete resolution persistence lead failed repair, fibrosis, chronic disease. Despite extensive research in animal models, translating preclinical findings therapies remains challenging, emphasizing need for integrated multiomic approaches advance AKI understanding treatment.

Язык: Английский

---

PU.1/Spi1 exacerbates ischemia-reperfusion induced acute kidney injury via upregulating Gata2 and promoting fibroblast activation

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

---

SOX9-dependent fibrosis drives renal function in nephronophthisis

EMBO Molecular Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 10, 2025

Abstract Fibrosis is a key feature of broad spectrum cystic kidney diseases, especially autosomal recessive disorders such as nephronophthisis (NPHP). However, its contribution to function decline and the underlying molecular mechanism(s) remains unclear. Here, we show that kidney-specific deletion Fbxw7 , recognition receptor SCF FBW7 E3 ubiquitin ligase, results in juvenile-adult NPHP-like pathology characterized by slow-progressing corticomedullary cysts, tubular degeneration, severe fibrosis, gradual loss function. Expression levels SOX9, known substrate FBW7, WNT4, potent pro-fibrotic factor downstream effector were elevated upon FBW7. Heterozygous Sox9 compound mutant mice led normalization WNT4 levels, reduced preservation without significant effects on dilatation degeneration. These data suggest FBW7-SOX9-WNT4-induced fibrosis drives NPHP and, possibly, other forms disorders.

Язык: Английский

---

Backtable Intra-Arterial Administration of C1 Esterase Inhibitor to Deceased Donor Kidney Allografts Improves Post-Transplant Allograft Function: Results of a Randomized Double-Blind Placebo-Controlled Clinical Trial

American Journal of Transplantation, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

---

Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis

Molecular Therapy, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

---

Single-cell RNA-seq uncovers lineage-specific regulatory alterations of fibroblasts and endothelial cells in ligamentum flavum hypertrophy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Май 15, 2025

Lumbar spinal stenosis (LSS) represents a major global healthcare burden resulting in back pain and disorders of the limbs among elderly population. The hypertrophy ligamentum flavum (HLF), marked by fibrosis inflammation, significantly contributes to LSS. Fibroblasts endothelial cells are two important pathological process (LF) inflammation. These exhibit heterogeneity various fibrotic diseases, yet their LF remains poorly defined. Using single-cell RNA-seq, we examined alterations fibroblasts, cells, key genes hypertrophic LF, aiming establish comprehensive atlas identify high-priority targets for pharmaceutical treatment Here, find there five distinct subpopulations fibroblasts: secretory-papillary, secretory-reticular, mesenchymal, pro-inflammatory, unknown. Importantly, HLF, proportion mesenchymal fibroblast increases compared normal (NLF), reflecting close association with pathogenesis HLF. Furthermore, critical target that might be involved HLF fibrosis, such as MGP, ASPN, OGN, LUM, CTSK, identified. In addition, also investigate highlight role AECs subpopulation fibrosis. This study will contribute our understanding offer possible diseases.

Язык: Английский

---

Interstitial Fibrosis in Kidney Allografts: Know Thy Enemy

Kidney International Reports, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

---

Mechanisms of Acute Kidney Injury–Chronic Kidney Disease Transition: Unraveling Maladaptive Repair and Therapeutic Opportunities

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

---