Abnormalities of IL-12 Family Cytokine Pathways in Autosomal Dominant Polycystic Kidney Disease Progression DOI Creative Commons
Corina Daniela Ene,

Ilinca Nicolae,

Cristina Căpușă

et al.

Medicina, Journal Year: 2024, Volume and Issue: 60(12), P. 1971 - 1971

Published: Nov. 30, 2024

Background and Objectives: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic renal disease with a complex physiopathology. More more studies sustain that inflammation plays crucial role in ADPKD pathogenesis progression. We evaluated IL-12 involvement pathophysiology by assessing serum levels of its monomers heterodimers. Materials Methods: A prospective case-control study was developed included 66 subjects control group 40 healthy subjects. The diagnosis based on familial history clinical imagistic exams. eGFR > 60 mL/min/1.73 mp, no hematuria or other disorders, stable blood pressure last 6 months. tested p40 p35 heterodimers p70, IL-23, IL 35, assessed ELISA method. Results: family programming abnormal patients. IL-12p70, IL-12p40, IL-23 secretion increased, while IL-12p35 IL-35 decreased compared to control. had progressive increase correlated immune response amplification, decrease eGFR, an TKV, albuminuria. On hand, were negatively CRP albuminuria positively advanced ADPKD. Conclusions: present investigated cytokine members’ pathogenesis, enriching our understanding common disorder.

Language: Английский

The role of M1/M2 macrophage polarization in the pathogenesis of obesity-related kidney disease and related pathologies DOI Creative Commons

Periklis Dousdampanis,

Ιωάννα Αγγελετοπούλου, Αthanasia Mouzaki

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 10, 2025

Obesity is a rapidly growing health problem worldwide, affecting both adults and children increasing the risk of chronic diseases such as type 2 diabetes, hypertension cardiovascular disease (CVD). In addition, obesity closely linked to kidney (CKD) by either exacerbating diabetic complications or directly causing damage. Obesity-related CKD characterized proteinuria, lipid accumulation, fibrosis glomerulosclerosis, which can gradually impair function. Among immune cells innate adaptive response involved in pathogenesis obesity-related diseases, macrophages play crucial role inflammation associated with CKD. obese individuals, enter pro-inflammatory state known M1 polarization, contributes inflammation. This polarization promotes tissue damage, fibrosis, leading progressive loss macrophage-induced oxidative stress key feature it also cell damage Macrophages contribute insulin resistance diabetes releasing inflammatory molecules that glucose metabolism, complicating management patients. Hypertension atherosclerosis, are often obesity, progression via pathways. influence blood pressure regulation vascular inflammation, particularly renin-angiotensin system. accumulate arterial plaques, plaque instability, may increase CVD review focuses on involvement highlights their critical link between other pathologies. Targeting macrophage ensuing could be an effective therapeutic strategy for related improve outcomes patients disease.

Language: Английский

Citations

2
An adoptive cell therapy with TREM2‐overexpressing macrophages mitigates the transition from acute kidney injury to chronic kidney disease DOI Creative Commons
Yating Zhang, Jie Liu, Siweier Luo

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: Feb. 25, 2025

Abstract Background Macrophages have been shown to contribute renal injury and fibrosis as well repair. Recently, Triggering Receptor Expressed on Myeloid Cells 2 (TREM2)‐positive macrophages play important roles in regulating tissue inflammation However, it remains unclear whether they can mitigate the transition from acute kidney chronic disease (the AKI–CKD transition). Methods The was generated by unilateral ischaemia–reperfusion (UIRI) wild‐type (WT) Trem2 knockout mice. F4/80 magnetic beads were used isolate macrophages. Flow cytometry determine levels of TREM2 CD11b levels. Quantitative reverse transcription polymerase chain reaction (qRT‐PCR), Western blotting histological staining performed expression cytokines fibrotic markers. RNA‐seq investigate transcriptomic changes between WT bone marrow‐derived (BMDMs). TREM2‐overexpressing using lentivirus transferred intravenously UIRI Results exhibited a strong protective effect transition. Genetic deletion resulted increased exacerbated Interestingly, we found that hypoxia could increase via HIF‐1α. Upregulated enhanced macrophage phagocytosis suppressed pro‐inflammatory cytokines, resulting lower apoptosis tubular epithelial cells. Using analysis, showed regulatory effects orchestrated PI3K‐AKT pathway. Pharmacological regulation pathway modulate macrophage‐mediated phagocytosis. In addition, an adoptive cell therapy effectively reduced immune infiltration, Conclusion Our study not only provides valuable mechanistic insights into role but also offers new avenue for macrophage‐based treat diseases. Key points worsens accelerates is upregulated HIF1α An reduces fibrosis.

Language: Английский

Citations

1
Network pharmacology and multi-omics validation of the Jianpi-Yishen formula in the treatment of chronic kidney disease DOI Creative Commons
Yuyan Li,

Yueming Luo,

Yilan Hu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 14, 2025

Objective Chronic kidney disease (CKD) is a major global health problem. In clinical practice, the Chinese patent herbal medicine Jianpi-Yishen (JPYS) formula commonly used to treat CKD. However, molecular mechanisms by which JPYS targets and modulates host immune response remain unclear. Methods This study utilized network pharmacology, RNA sequencing (RNA-seq), metabolic analyses using in vivo vitro models investigate impact of on inflammation system. Specifically, focused macrophage polarization changes that may slow down progression Results A total 14,946 CKD-related were identified from GeneCards Online Mendelian Inheritance Man (OMIM) databases through pharmacology analyses. 227 potential predicted TCMSP database. Additionally, diagram demonstrated 11 associated with activity. studies indicated could reduce blood urea nitrogen serum creatinine adenine-induced CKD rats. Furthermore, inhibited inflammatory damage abnormal infiltration this model. RNA-seq, proteomic regulation amino acid metabolism betaine, specifically referring glycine, serine, threonine metabolism, as key target slowing addition, suggested enhance tryptophan M1 betaine M2 polarization. Conclusions The has been shown have beneficial CKD; mechanism mitigation interaction between Of specific importance context are roles

Language: Английский

Citations

0
Multiple omics-based machine learning reveals specific macrophage sub-clusters in renal ischemia-reperfusion injury and constructs predictive models for transplant outcomes DOI
Jiyue Wu, Feilong Zhang, Zhen Li

et al.

Computational Biology and Chemistry, Journal Year: 2025, Volume and Issue: 117, P. 108421 - 108421

Published: March 12, 2025

Language: Английский

Citations

0
Ultraviolet-treated riboflavin alleviates atopic dermatitis by inhibiting NLRP3 inflammasome activation and M1 macrophage polarization via histone lactylation DOI Creative Commons
Shuang Ge,

Bingquan Qiu,

Rong Liu

et al.

Biochemical Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 116879 - 116879

Published: March 1, 2025

Language: Английский

Citations

0
Toll-Like Receptors in Kidney Ischemia-Reperfusion Injury: Modulating Macrophage Responses for Therapeutic Insights DOI

H. Malathi,

Gaurav Khandelwal,

S Gayathri

et al.

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: unknown, P. 155940 - 155940

Published: March 1, 2025

Language: Английский

Citations

0
Pyroptosis for osteoarthritis treatment: insights into cellular and molecular interactions inflammatory DOI Creative Commons
Minghui Lin, Cunxin Zhang, Haiming Li

et al.

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

Published: April 1, 2025

Osteoarthritis (OA) is a widely prevalent chronic degenerative disease often associated with significant pain and disability. It characterized by the deterioration of cartilage extracellular matrix (ECM), synovial inflammation, subchondral bone remodeling. Recent studies have highlighted pyroptosis-a form programmed cell death triggered inflammasome-as key factor in sustaining inflammation. Central to this process are inflammatory cytokines interleukin-1β (IL-1β) interleukin-18 (IL-18), which play crucial roles mediating intra-articular pyroptosis through NOD-like receptor protein 3 (NLRP3) inflammasome. This paper investigates role pathway perpetuating diseases its linkage OA. Furthermore, it explores mechanisms pyroptosis, mediated nuclear κB (NF-κB), purinergic P2X ligand-gated ion channel 7 (P2X7R), adenosine monophosphate (AMP)-activated kinase (AMPK), hypoxia-inducible factor-1α (HIF-1α). Additionally, examines interactions among various cellular components context These insights indicate that targeting regulation presents promising therapeutic approach for prevention treatment OA, offering valuable theoretical perspectives effective management.

Language: Английский

Citations

0
Friend or foe? The role of SIRT6 on macrophage polarized to M2 subtype in acute kidney injury to chronic kidney disease DOI Creative Commons

Gao Xiaoqin,

Xuemei Liu, Zhaodi Han

et al.

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: April 22, 2025

Acute kidney injury (AKI) substantially increases the risk of developing and worsening chronic disease (CKD). The shift from AKI to CKD is a complex process that involves various cell types, with macrophages playing key role in responding renal injury. M1 M2 macrophages-the two main types macrophages-have distinct functions at stages. induce damage by secreting pro-inflammatory cytokines immediately after injury, whereas subsequently facilitate tissue repair. conversion subtype vital for effective repair However, when infiltrate persistently, they can paradoxically cause fibrosis, thereby complicating recovery. As epigenetic regulatory factor, deacetylase SIRT6 exerts biological effects through its enzymatic reactions, including regulation cellular metabolism, antioxidant stress response, inhibition fibrosis. expressed all major resident cells demonstrated protect kidneys. promotes transition subtype; nevertheless, this poses fibrosis if remain because influence SIRT6. This review aimed (i) delve into intricate macrophage polarization toward context progression (ii) explore potential strategies may effectively target mitigate CKD.

Language: Английский

Citations

0
Macrophage Depletion Alleviates Immunosenescence in Diabetic Kidney by Modulating GDF-15 and Klotho DOI Open Access
Asma S. Alonazi,

Rana M. Aloraini,

Lama M. Albulayhi

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 3990 - 3990

Published: April 23, 2025

Cellular senescence is a hallmark of aging and contributes to age-related diseases, including diabetic nephropathy (DN). Additionally, macrophage-mediated inflammation has been linked with DKD. Therefore, we investigated the effect macrophage depletion on kidney cell in DN, focusing relationship between GDF-15 Klotho signaling pathways. Wistar albino rats (n = 24) were divided into four groups: healthy control, liposomal clodronate (LC)-treated healthy, diabetic, LC-treated groups. Rats groups intravenously administered LC once week for 4 weeks. Rat models type 2 diabetes successfully established via administration streptozotocin high-fat diet, as evidenced by increased blood glucose levels, weight body (KW/BW) ratio, serum albumin, creatinine, urea damage, oxidative stress. However, LC-mediated reduced KW/BW improved parameters, decreased inflammatory markers (IL-6 TNF-α), ameliorated treatment promoted polarization towards anti-inflammatory phenotype, downregulated expression, upregulated damage. In conclusion, combats modulating GDF-15, indicating their potential novel targets DN treatment.

Language: Английский

Citations

0
Alleviation of doxorubicin-induced nephrotoxicity in breast cancer mice by using combination of green tea and moringa: Focus on antioxidant, apoptosis, inflammation, and histopathological insights DOI Creative Commons

Abas H. Laftah,

Nawfal Alhelfi, Sadeq Ka. Al-Salait

et al.

Food systems, Journal Year: 2025, Volume and Issue: 8(1), P. 4 - 15

Published: April 25, 2025

Doxorubicin (DXR)-induced nephrotoxicity remains a major concern in cancer treatment and calls for potential prevention of kidney injury. This study aims to evaluating the nephroprotective potentials green tea moringa used as 1% 2% water extracts DXR‑induced damage female Balb/C mice with breast cancer. Thirty six were divided into groups follows: healthy control; 4T1 cells cancer-induced; DXR treatment; cancer-induced under DOX treated combination; combination. The variables experiment body weight, tumor volume, antioxidant enzyme activities (CAT, GPx, SOD), oxidative stress markers (TOS, TAC, OSI), pro-inflammatory cytokines (IL‑1, TNF‑α), apoptosis inflammation-related genes (BAX, BCL2, NLRP3, NFKB). Histological analysis kidneys was also done check cellular changes. led decrease weight an increase enzymes, which is indication damage. levels these enzymes significantly lowered by combination herbal extracts, especially at 2%, indicating properties. brought back normal reduced through raising CAT, SOD decreasing TOS OSI levels. Furthermore, decreased affected related gene expressions; BAX down-regulated BCL2 up-regulated, helped increasing cell survival inflammation. NLRP3/NFKB DXR‑treated dose dependent manner. Based on results, mixture leaf aqueous (1:1 ratio) can be considered appropriate reduce DOX‑induced injury patients.

Language: Английский

Citations

0