Mesenchymal Stem Cell-Derived Exosomes Ameliorate Diabetic Kidney Disease Through the NLRP3 Signaling Pathway

Stem Cells, Journal Year: 2023, Volume and Issue: 41(4), P. 368 - 383

Published: Jan. 21, 2023

Diabetic kidney disease (DKD) is the leading cause of end-stage renal worldwide. Exosomes (Exo) derived from human umbilical cord mesenchymal stem cells (HUC-MSCs) have been demonstrated to be an effective therapy for DKD, but underlying mechanisms this action remain poorly defined. We investigated association DKD with inflammasome activation and pathophysiological relevance Exo-mediated inflammation relief as well damage repair in progression. co-cultured podocytes HUC-MSCs Exo (MSCs-Exo) under high glucose (HG) injected MSCs-Exo into diabetic mice, then we detected NLRP3 both vitro vivo. found that HG reduced viability podocytes, activated signaling pathway increased mice. attenuated inflammation, including expression IL-6, IL-1β, IL-18, TNF-α; depressed ameliorated injury. Furthermore, miR-22-3p, which relatively highly expressed miRNAs exosomes MSCs, may key point progress, by suppressing its known target, NLRP3. Knocking down miR-22-3p abolished their anti-inflammation activity beneficial function Collectively, our results transferring protected mice mediating inflammasome, indicating MSC-derived a promising therapeutic cell-free strategy DKD.

Language: Английский

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Promoting vascularized bone regeneration via strontium-incorporated hydroxyapatite bioceramic

Materials & Design, Journal Year: 2023, Volume and Issue: 234, P. 112313 - 112313

Published: Sept. 9, 2023

Language: Английский

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Nrf2 activation: a key mechanism in stem cell exosomes-mediated therapies

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: March 2, 2024

Abstract Exosomes are nano-sized membrane extracellular vesicles which can be released from various types of cells. originating inflammatory or injured cells have detrimental effects on recipient cells, while exosomes derived stem not only facilitate the repair and regeneration damaged tissues but also inhibit inflammation provide protective against diseases, suggesting they may serve as an alternative strategy transplantation. a fundamental role in communication between through transfer proteins, bioactive lipids nucleic acids (like miRNAs mRNAs) This significantly impacts both physiological pathological functions Nuclear factor erythroid 2–related 2 (Nrf2), transcription factor, is able to mitigate damage caused by oxidative stress signaling pathways. The positive resulting activation Nrf2 pathway different disorders been documented literature. Studies confirmed that could act effective agonists. However, limited studies explored therapeutic cell-derived exosomes. review provides comprehensive overview existing knowledge concerning pathways impact exerted cell some common diseases. Graphical

Language: Английский

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A Narrative Review of New Treatment Options for Diabetic Nephropathy

Cureus, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Diabetic nephropathy (DN) is a type of that caused by diabetic condition. seen in 1 and 2 diabetes. End-stage renal disorders are brought on DN. thought to be linked metabolic changes the body. Proteinuria glomerular filtration rate two most crucial diagnostic prognosis measures for kidney disease (DKD), yet both have significant disadvantages. Novel biomarkers thus increasingly required improve risk factors detect at an early stage. Controlling blood glucose vital sign like body temperature pressure, reducing cholesterol levels, blocking renin-angiotensin system standard treatments patients. On other hand, if used too late within course disease, these therapeutic techniques can only provide partial relief from nephropathy. The complicated pathophysiology kidney, which experiences variety severe structural, metabolic, functional alterations, represents one important obstacles event effective therapeutics Despite issues, new diabetes models identified promising treatment targets identifying mechanisms control functions podocytes endothelial cells. It has been shown vast majority trials inhibitors combined with integrative therapies work well Combining sodium-glucose cotransporter-2 renin-angiotensin-aldosterone blockers novel way slow down DKD lowering inflammatory fibrotic indicators hyperglycemia, more than using either medicine alone. Aldosterone receptor advanced glycation end-product recently produced medications may successfully treat

Language: Английский

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Thread-structural microneedles loaded with engineered exosomes for annulus fibrosus repair by regulating mitophagy recovery and extracellular matrix homeostasis

Bioactive Materials, Journal Year: 2024, Volume and Issue: 37, P. 1 - 13

Published: March 13, 2024

Low back pain is among the most grave public health concerns worldwide and major clinical manifestation of intervertebral disc degeneration (IVDD). The destruction annulus fibrosus (AF) primary cause IVDD. A sustainable stable treatment system for IVDD lacking because special organizational structure low nutrient supply AF. We here found that results in impaired mitochondrial function AF tissue, autophagy (mitophagy) plays a protective role this process. therefore reported thread-structural microneedle (T-MN) matching ring Based on adsorption effect laminin, our T-MN could load with bone marrow mesenchymal stem cell-derived exosomes to envelope regulating mitophagy microRNA (miRNA 378), named as

Language: Английский

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Fatty Acid β-Oxidation in Kidney Diseases: Perspectives on Pathophysiological Mechanisms and Therapeutic Opportunities

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: April 20, 2022

The kidney is a highly metabolic organ and requires large amount of ATP to maintain its filtration-reabsorption function, mitochondrial fatty acid β-oxidation serves as the main source energy meet functional needs. Reduced inefficient thought be major mechanism contributing diseases, including acute injury, chronic disease diabetic nephropathy. PPARα, AMPK, sirtuins, HIF-1, TGF-β/SMAD3 activation have all been shown play key roles in regulation restoration by modulation these molecules can ameliorate development such diseases. Here, we disentangle lipid metabolism properties potential mechanisms mesenchymal stem cells their extracellular vesicles, emphasize role on metabolism. This review aims highlight important progression explore effects therapeutic for

Language: Английский

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Exosomal miR‐7002‐5p derived from highglucose‐induced macrophages suppresses autophagy in tubular epithelial cells by targeting Atg9b

The FASEB Journal, Journal Year: 2022, Volume and Issue: 36(9)

Published: Aug. 16, 2022

Abstract Macrophage infiltration plays an important role in the progression of diabetic nephropathy (DN). Previously, we demonstrated that highglucose‐stimulated macrophage‐derived exosomes (HG‐exo) induces proliferation and extracellular matrix accumulation glomerular mesangial cells, but its effect on tubular cells is unclear. This study aimed to explore HG‐exo renal injury DN. The results show could induce dysfunction, autophagy inhibition, inflammation mouse epithelial cell (mTEC) C57 kidney. Moreover, miR‐7002‐5p was differentially expressed based miRNAs sequencing bioinformatics analysis. A dual‐luciferase reporter assay confirmed Atg9b direct target gene miR‐7002‐5p. Further experimentation showed inhibition vivo vitro reserves effects. These carries excessive inhibits through targeting Atg9b; this process then dysfunction inflammation. In conclusion, our clarifies DN expected provide new insight prevention treatment.

Language: Английский

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Roles of exosomes and exosome-derived miRNAs in pulmonary fibrosis

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 11, 2022

Pulmonary fibrosis is a chronic, progressive fibrosing interstitial lung disease of unknown etiology that leads rapidly to death. It characterized by the replacement healthy tissue through an altered extracellular matrix and damage alveolar structure. New pharmacological treatments biomarkers are needed for pulmonary ensure better outcomes earlier diagnosis patients. Exosomes nanoscale vesicles released nearly all cell types play central role as mediators cell-to-cell communication. Moreover, exosomes emerging crucial factor in antigen presentation, immune response, immunomodulation, inflammation, cellular phenotypic transformation have also shown promising therapeutic potential fibrosis. This review summarizes current knowledge may promote be utilized diagnostics prognostics. In addition, utilization their cargo miRNAs novel therapeutics mechanisms discussed. aims elucidate pathogenesis paves way developing Further in-depth research clinical trials on this topic encouraged future.

Language: Английский

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Intravenous injection of human umbilical cord-derived mesenchymal stem cells ameliorates not only blood glucose but also nephrotic complication of diabetic rats through autophagy-mediated anti-senescent mechanism

Stem Cell Research & Therapy, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 29, 2023

Abstract Background Diabetic nephropathy (DN) is one of the most severe complications diabetes mellitus, which characterized by early occurrence albuminuria and end-stage glomerulosclerosis. Senescence autophagy podocytes play an important role in DN development. Human umbilical cord-derived mesenchymal stem cells (hucMSCs) have potential treatment its complications. However, hucMSCs underlying mechanism remain unclear. Methods In vivo, a streptozotocin-induced diabetic male Sprague Dawley rat model was established to determine renoprotective effect on biochemical analysis, histopathology, immunohistochemical staining renal tissues. And distribution various organs rats within 168 h analyzed. vitro, CCK8 assay, wound healing β-galactosidase were conducted detect beneficial effects high glucose-induced podocytes. Real-time PCR western blot assays applied explore action hucMSCs. Results The vivo data revealed that distributed into kidneys significantly protected from damage. vitro indicated improved cell viability, healing, senescence glucose-damaged through paracrine mode. Besides, altered expressions senescence-associated genes ( p16 , p53 p21 ) autophagy-associated Beclin-1 p62 LC3 Mechanistically, injury activating attenuating AMPK/mTOR pathway. Conclusions conclusion, might be promising therapeutic strategy for clinical DN-induced damages.

Language: Английский

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Research progress on exosomes in podocyte injury associated with diabetic kidney disease

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: March 20, 2023

Diabetic kidney disease (DKD), a common cause of end-stage renal disease, is serious complication that develops with the progression chronic diabetes. Its main clinical manifestations are persistent proteinuria and/or progressive decline in estimated glomerular filtration rate. Podocytes, terminally differentiated visceral epithelial cells, constitute barrier together basement membrane and endothelial structural functional integrity closely related to proteinuria. In recent years, an increasing number studies have confirmed podocyte injury central target occurrence development DKD, research on exosomes associated DKD has also made great progress. The aim this review comprehensively describe potential diagnostic value analyze mechanism by which realize communication between podocytes other types cells discuss possibility as targeted therapy drug carriers provide new targets for insights into delaying treating DKD.

Language: Английский

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