Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances

Journal of Translational Medicine, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 9, 2023

Abstract Cancer remains the leading cause of death around world. In cancer treatment, over 50% patients receive radiotherapy alone or in multimodal combinations with other therapies. One adverse consequences after radiation exposure is occurrence radiation-induced tissue fibrosis (RIF), which characterized by abnormal activation myofibroblasts and excessive accumulation extracellular matrix. This phenotype can manifest multiple organs, such as lung, skin, liver kidney. In-depth studies on mechanisms have shown that a variety signals immune cells release cytokines, intracellular cGAS/STING, oxidative stress response, metabolic reprogramming proteasome pathway are involved myofibroblasts. Tissue extremely harmful to patients' health requires early diagnosis. addition traditional serum markers, histologic imaging tests, diagnostic potential nuclear medicine techniques emerging. Anti-inflammatory antioxidant therapies treatments for fibrosis. Recently, some promising therapeutic strategies emerged, stem cell therapy targeted However, incomplete knowledge hinders treatment this disease. Here, we also highlight mechanistic, directions

Language: Английский

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Role of peroxisomes in the pathogenesis and therapy of renal fibrosis

Metabolism, Journal Year: 2025, Volume and Issue: 166, P. 156173 - 156173

Published: Feb. 22, 2025

Language: Английский

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Inhibition of PFKP in renal tubular epithelial cell restrains TGF-β induced glycolysis and renal fibrosis

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(12)

Published: Dec. 12, 2023

Abstract Metabolic reprogramming to glycolysis is closely associated with the development of chronic kidney disease (CKD). Although it has been reported that phosphofructokinase 1 (PFK) a rate-limiting enzyme in glycolysis, role platelet isoform PFK (PFKP) fibrosis initiation and progression as yet poorly understood. Here, we investigated whether PFKP could mediate interstitial by regulating proximal tubular epithelial cells (PTECs). We induced overexpression or knockdown renal tubules via an adeno-associated virus (AAV) vector kidneys mice following unilateral ureteral occlusion. Our results show dilated tubules, area fibrosis, were promoted tubule-specific PFKP, repressed PFKP. Furthermore, expression restrained, while TGF-β1-induced human PTECs line. Mechanistically, Chip-qPCR revealed TGF-β1 recruited small mothers against decapentaplegic (SMAD) family member 3-SP1 complex promoter enhance its expression. Treatment isorhamnetin notably ameliorated PTEC-elevated fibrosis. Hence, our suggest mediates PTECs.

Language: Английский

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Integrative transcriptomic and proteomic profile revealed inhibition of oxidative phosphorylation and peroxisomes during renal interstitial fibrosis

Journal of Proteomics, Journal Year: 2024, Volume and Issue: 298, P. 105144 - 105144

Published: Feb. 29, 2024

Effective therapies of chronic kidney disease (CKD) are lacking due to the unclear molecular pathogenesis. Previous single omics-studies have described potential regulation mechanism CKD only at level transcription or translation. Therefore, this study generated an integrated transcriptomic and proteomic profile provide deep insights into continuous transcription-translation process during CKD. The comprehensive datasets identified 14,948 transcripts 6423 proteins, 233 up-regulated 364 down-regulated common differentially expressed genes transcriptome proteome were selected further combined bioinformatics analysis. obtained results revealed reactive oxygen species (ROS) metabolism antioxidant system imbalance mitochondria peroxisomes significantly repressed in Overall, presents a valuable multi-omics analysis that sheds light on mechanisms underlying Chronic is progressive irreversible condition abnormal function structure, ranked 18th among leading causes death globally, significant societal burden. Hence, there urgent need for research detect new, sensitive, specific biomarkers. Omics-based studies offer great identify mechanisms, aid clinical diagnosis, develop novel treatment strategies mainly focused gene expression protein synthesis CKD, thereby compelling us conduct meticulous data from UUO mouse model. Here, we performed unified model by integrating transcriptomes suites first time. Our contributes deeper understanding pathogenesis provides basis subsequent management drug development.

Language: Английский

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Mitochondrial dysfunction in acute kidney injury

Renal Failure, Journal Year: 2024, Volume and Issue: 46(2)

Published: Aug. 27, 2024

Acute kidney injury (AKI) is a systemic clinical syndrome increasing morbidity and mortality worldwide in recent years. Renal tubular epithelial cells (TECs) death caused by mitochondrial dysfunction one of the pathogeneses. The imbalance quality control main cause dysfunction. Mitochondrial plays crucial role AKI. mechanisms are involved regulating integrity function, including antioxidant defense, control, DNA (mtDNA) repair, dynamics, mitophagy, biogenesis. Currently, many studies have used as targeted therapeutic strategy for Therefore, this review aims to present latest research advancements on AKI, providing valuable reference theoretical foundation prevention treatment condition, ultimately enhancing patient prognosis.

Language: Английский

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Deletion of Pyruvate Carboxylase in Tubular Epithelial Cell Promotes Renal Fibrosis by Regulating SQOR/cGAS/STING‐Mediated Glycolysis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract Renal fibrosis is a common pathway involved in the progression of various chronic kidney diseases to end‐stage renal disease. Recent studies show that mitochondrial injury tubular epithelial cells (RTECs) crucial pathological foundation for fibrosis. However, underlying regulatory mechanisms remain unclear. Pyruvate carboxylase (PC) catalytic enzyme located within mitochondria intricately linked with damage and metabolism. In present study, downregulation PC fibrotic animal human samples demonstrated. proximal tubule–specific Pcx gene knockout mice ( cKO ) has significant interstitial compared control mice, heightened expression extracellular matrix molecules. This further demonstrated stable knock‐out RTEC line. Mechanistically, deficiency reduces its interaction sulfide:quinone oxidoreductase (SQOR), increasing ubiquitination degradation SQOR. leads morphological functional disruption, increased mtDNA release, activation cGAS‐STING pathway, elevated glycolysis levels, ultimately, promotes study investigates molecular through which induces metabolic reprogramming RTECs. provides novel theoretical potential therapeutic targets pathogenesis treatment

Language: Английский

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The Role and Mechanisms of Aurora Kinases in Kidney Diseases

Clinical Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Aurora kinases are a family of serine/threonine that includes kinase A, B, and C. These play crucial roles in mitotic spindle formation cell proliferation. Over the past several decades, extensive research has elucidated multifaceted cancer development progression. Recent studies have also highlighted significant involvement various kidney diseases, such as renal carcinoma, diabetic nephropathy, chronic disease, polycystic disease. The mechanisms by which contribute to diseases complex influenced both specific pathological conditions environmental factors. In this review, we comprehensively summarize role through operate discuss efficacy application existing inhibitors targeting these managing disorders animal models.

Language: Английский

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p16INK4a Deletion Alleviated Obesity‐Associated Kidney Fibrosis by Regulating Metabolic Reprogramming and the Inflammasome Pathway

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(5)

Published: March 1, 2025

ABSTRACT Recent research has revealed a close association between obesity and various metabolic disorders, including renal diseases, but the mechanism is still unknown. This study explored role of p16INK4a in obesity‐related kidney fibrosis evaluated its potential as therapeutic target. Using wild‐type (WT) mice p16 KO mice, we fed both groups high‐fat diet (HFD) for 6 months. Our results showed that an HFD led to significant weight gain increased expression WT mouse kidneys. Notably, presented reduced fibrosis, indicated by decreased levels profibrotic proteins (α‐SMA collagen I) improved histological outcomes, glomeruli tubules. P16 also suppressed several proinflammatory biomarkers (MMP1, MMP3, IL‐1β, TNF‐α IL‐6) inhibited NLRP3 inflammasome pathway. The administration ABT263 further validated these findings decreasing inflammation HFD‐fed suggesting contributes fibrotic inflammatory processes. Metabolomic analyses knockout influenced pathways, linoleic acid pyrimidine metabolism, HFD‐induced Additionally, over‐expression was observed kidneys chronic disease patients with long‐term hyperlipidaemia. These highlight critical obesity‐induced damage suggest targeting may be promising approach treating inflammation.

Language: Английский

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Diosmin Attenuates UUO-induced Renal Ferroptosis and Fibrosis by Inhibiting the HIF-1α/FABP4 Signaling Axis

Phytomedicine, Journal Year: 2025, Volume and Issue: unknown, P. 156738 - 156738

Published: April 1, 2025

Language: Английский

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Fermented Strawberry (Fragaria x Ananassa Duch.) Mitigates Renal Fibrosis in a Unilateral Ureteral Obstruction Model by Reducing Inflammation, Oxidative Stress, and Regulating Smad Signaling

Journal of Medicinal Food, Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Renal fibrosis is a common outcome in many progressive renal diseases. Unilateral ureteral obstruction (UUO) known to induce oxidative stress and inflammation the kidneys, leading development of fibrosis. Fermented strawberry (Fragaria x ananassa Duch.) possesses antioxidant properties; however, its effect on remains unclear. This study aimed evaluate impact fermented dry powder (FSP) by assessing proinflammatory cytokines, markers, underlying mechanisms. Male Sprague-Dawley rats were subjected UUO surgery tubulointerstitial obstructive nephropathy. Ten days postsurgery, randomly divided into four groups (n = 6), including sham-operated control group. FSP was administered orally at doses 0.05 or 0.5 g kg-1 body weight daily for 21 days. treatment significantly improved function, reduced tubular dilation, decreased interstitial volume rats. levels tumor necrosis factor-α interleukin-6, while enhancing activities enzymes such as superoxide dismutase catalase. Treatment with resulted reduction collagen deposition kidneys 49% 69%, respectively, compared increased E-cadherin expression α-smooth muscle actin level Furthermore, transforming growth factor-β Smad2/3 upregulating Smad7 expression. These findings suggest that mitigates fibrosis, likely through modulation Smad signaling attenuation inflammation.

Language: Английский

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