Human Umbilical Cord Mesenchymal Stem Cells Inhibit Pyroptosis of Renal Tubular Epithelial Cells through miR-342-3p/Caspase1 Signaling Pathway in Diabetic Nephropathy

Stem Cells International, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 12

Published: April 4, 2023

Diabetic nephropathy (DN) is one of the microvascular complications diabetes. Recent studies suggest that pyroptosis renal tubular epithelial cell plays a critical role in DN. Currently, effective therapeutic strategies to counteract and reverse progression DN are lacking. Mesenchymal stem cells (MSCs) represent an attractive tool for tissue damage inflammation owing their unique immunomodulatory properties. However, underlying mechanisms remain largely unknown. In present study, we found human umbilical cord MSCs (UC-MSCs) can effectively ameliorate kidney reduce rats. Importantly, UC-MSC treatment inhibits inflammasome-mediated Mechanistically, performed RNA sequencing identified miR-342-3p was significantly downregulated kidneys Furthermore, negatively correlated with injury The expression increased after treatment. Moreover, decreased Caspase1 by targeting its 3'-UTR, which confirmed double-luciferase assay. Using miRNA mimic transfection, demonstrated UC-MSC-derived inhibited through NLRP3/Caspase1 pathway. These findings would provide novel intervention strategy use miRNA-modified therapy diseases.

Language: Английский

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Pharmacological roles of lncRNAs in diabetic retinopathy with a focus on oxidative stress and inflammation

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 214, P. 115643 - 115643

Published: June 13, 2023

Language: Английский

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Pyroptosis: A New Insight Into Eye Disease Therapy

Frontiers in Pharmacology, Journal Year: 2021, Volume and Issue: 12

Published: Dec. 3, 2021

Pyroptosis is a lytic form of programmed cell death mediated by gasdermins (GSDMs) with pore-forming activity in response to certain exogenous and endogenous stimuli. The inflammasomes are intracellular multiprotein complexes consisting pattern recognition receptors, an adaptor protein ASC (apoptosis speck-like protein), caspase-1 cause autocatalytic activation caspase-1, which cleaves gasdermin D (GSDMD), inducing pyroptosis accompanied cytokine release. In recent years, the pathogenic roles multiple eye diseases, including keratitis, dry eyes, cataracts, glaucoma, uveitis, age-related macular degeneration, diabetic retinopathy, have been continuously confirmed. Inhibiting inflammasome abnormal eyes generally attenuates inflammation benefits prognosis. Therefore, insight into pathogenesis underlying development various types diseases may provide new therapeutic strategies for ocular disorders. Inhibitors pyroptosis, such as NLRP3, GSDMD inhibitors, proven be effective many diseases. purpose this article illuminate mechanism emphasize its crucial role addition, we review application modulators

Language: Английский

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Role of pyroptosis in diabetic retinopathy and its therapeutic implications

European Journal of Pharmacology, Journal Year: 2021, Volume and Issue: 904, P. 174166 - 174166

Published: May 9, 2021

Language: Английский

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Autophagy in the retinal neurovascular unit: New perspectives into diabetic retinopathy

Journal of Diabetes, Journal Year: 2023, Volume and Issue: 15(5), P. 382 - 396

Published: March 2, 2023

Abstract Diabetic retinopathy (DR) is one of the most prevalent retinal disorders worldwide, and it a major cause vision impairment in individuals productive age. Research has demonstrated significance autophagy DR, which critical intracellular homeostasis mechanism required for destruction recovery cytoplasmic components. Autophagy maintains physiological function senescent impaired organelles under stress situations, thereby regulating cell fate via various signals. As retina's functional fundamental unit, neurovascular unit (NVU) keeping environment's stability supporting needs metabolism. However, essential normal NVU structure function. We discuss strong association between DR this review, as well many kinds its crucial activities retina. By evaluating pathological changes latest advancements molecular mechanisms that may be involved pathophysiology NVU, we seek to propose new ideas methods prevention treatment DR.

Language: Английский

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Exosomal lncRNA-MIAT promotes neovascularization via the miR-133a-3p/MMP-X1 axis in diabetic retinopathy

Experimental Eye Research, Journal Year: 2024, Volume and Issue: 243, P. 109912 - 109912

Published: April 24, 2024

Language: Английский

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MALAT1 knockdown alleviates the pyroptosis of microglias in diabetic cerebral ischemia via regulating STAT1 mediated NLRP3 transcription

Molecular Medicine, Journal Year: 2023, Volume and Issue: 29(1)

Published: April 3, 2023

Abstract Background Dysregulated long non-coding RNAs participate in the development of diabetic cerebral ischemia. This study aimed to investigate underlying mechanism lncRNA MALAT1 Method Middle artery occlusion (MCAO) was performed establish I/R vivo. TTC and neurological deficits assessment were assess ischemic injury. LDH conducted detect cytotoxicity. RT-qPCR western blotting assays applied determine mRNA protein expression. Flow cytometry pyroptosis BV2 cells. Immunofluorescence FISH for subcellular localization STAT1. ELISA cytokine release. Dual luciferase reporter, RIP, ChIP used validate interaction between STAT1 MALAT1/NLRP3. Diabetes aggravated injury vivo vitro. Diabetic ischemia induced inflammatory response inflammation-induced cell pyroptosis. Result overexpressed models However, knockdown suppressed Moreover, interacted with transcriptionally activate NLRP3. Knockdown significantly reversed effects MALAT1. Furthermore, promotes transcription. interacts promote microglias by through activating NLRP3 Conclusion Thus, may be a potential promising therapy target

Language: Английский

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The role of ncRNAs‐mediated pyroptosis in diabetes and its vascular complications

Cell Biochemistry and Function, Journal Year: 2024, Volume and Issue: 42(2)

Published: March 1, 2024

Abstract Over the past decade, prevalence of diabetes has increased significantly worldwide, leading to an increase in vascular complications (VCD), such as diabetic cardiomyopathy (DCM), nephropathy (DN), and retinopathy (DR). Noncoding RNAs (ncRNAs), microRNAs (miRNAs), long (lncRNAs), circular (circRNAs), play a key role cellular processes, including pathophysiology VCD via pyroptosis. ncRNAs (e.g., miR‐17, lnc‐MEG3, lnc‐KCNQ1OT1) can regulate pyroptosis pancreatic β cells. Some are involved progression. For example, miR‐21, lnc‐KCNQ1OT1, lnc‐GAS5, lnc‐MALAT1 were reported DN DCM, lnc‐MIAT was identified DCM DR. Herein, this review aimed summarize recent research findings related ncRNAs‐mediated at onset progression VCD.

Language: Английский

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Epigenetic modifications and metabolic memory in diabetic retinopathy: beyond the surface

Neural Regeneration Research, Journal Year: 2022, Volume and Issue: 18(7), P. 1441 - 1441

Published: Nov. 18, 2022

Epigenetics focuses on DNA methylation, histone modification, chromatin remodeling, noncoding RNAs, and other gene regulation mechanisms beyond the sequence. In past decade, epigenetic modifications have drawn more attention as they participate in development progression of diabetic retinopathy despite tight control glucose levels. The underlying still urgently need to be elucidated. condition facilitates changes influences target expression. this review, we summarize involvement metabolic memory propose novel insights into treatment retinopathy.

Language: Английский

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Long Noncoding RNA MIAT Regulates Hyperosmotic Stress-Induced Corneal Epithelial Cell Injury via Inhibiting the Caspase-1-Dependent Pyroptosis and Apoptosis in Dry Eye Disease

Journal of Inflammation Research, Journal Year: 2022, Volume and Issue: Volume 15, P. 3269 - 3283

Published: June 1, 2022

Purpose: The biological role and mechanism of long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) in dry eye remain to be illustrated. Pyroptosis is a noticeable form inflammatory activation, which characteristic gasdermin D (GSDMD)-driven cell death. present study was designed explore the MIAT pyroptosis apoptosis induced by hyperosmolarity stress (HS) human corneal epithelial cells (HCECs). Methods: HCECs were cultured 70– 120 mM hyperosmotic medium for 24 h create model vitro. level marker GSDMD measured, response evaluated detecting IL-1β IL-18 levels. Exogenous caspase-1 inhibitor Ac-YVAD-CHO used. examined activity, immunofluorescent staining, Western blotting. Flow cytometry performed test rate HCECs. Cell migration proliferation detected. expression lncRNA detected quantitative real-time PCR. knocked down small interfering (siRNA) transfection. effects inhibition on pyroptosis, apoptosis, migration, observed. Results: HS promoted elevating caspase-1, GSDMD, active cleavage (N-terminal domain, N-GSDMD), increased release IL-1β, IL-18, LDH with reduced migration. These changes prevented caspase-1. significantly exposed medium. Silencing chemokines while inhibiting Conclusion: involved HS-induced provides new understanding pathogenesis eye. Keywords: transcript, eye,

Language: Английский

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