Macrophages communicate with mesangial cells through the CXCL12/DPP4 axis in lupus nephritis pathogenesis

Cell Death and Disease, Год журнала: 2024, Номер 15(5)

Опубликована: Май 18, 2024

Abstract Lupus nephritis (LN) occurs in 50% of cases systemic lupus erythematosus (SLE) and is one the most serious complications that can occur during progression. Mesangial cells (MCs) are intrinsic kidney regulate capillary blood flow, phagocytose apoptotic cells, secrete vasoactive substances growth factors. Previous studies have shown various types inflammatory activate MCs for hyperproliferation, leading to disruption filtration barrier impairment renal function LN. Here, we characterized heterogeneity LN mice by single-nucleus RNA sequencing (snRNA-seq) revealed interaction between macrophages through CXC motif chemokine ligand 12 (CXCL12)/dipeptidyl peptidase 4 (DPP4) axis. In culture, modulated proliferation migration this ligand–receptor interaction. mice, treatment with linagliptin, a DPP4 inhibitor, effectively inhibited MC reduced urinary protein levels. Together, our findings indicated targeting CXCL12/DPP4 axis linagliptin may serve as novel strategy via

Язык: Английский

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Berberine regulates mesangial cell proliferation and cell cycle to attenuate diabetic nephropathy through the PI3K/Akt/AS160/GLUT1 signalling pathway

Journal of Cellular and Molecular Medicine, Год журнала: 2022, Номер 26(4), С. 1144 - 1155

Опубликована: Янв. 9, 2022

Abstract High glucose (HG) is one of the basic factors diabetic nephropathy (DN), which leads to high morbidity and disability. During DN, expression glomerular transporter 1 (GLUT1) increases, but relationship between HG GLUT1 unclear. Glomerular mesangial cells (GMCs) have multiple roles in HG‐induced DN. Here, we report prominent dysfunction, especially GMC abnormalities, DN mice, closely related alteration. In vivo studies shown that BBR can alleviate pathological changes abnormal renal function indicators mice. vitro, (30, 60 90 μmol/L) not only increased proportion G1 phase also reduced S under conditions at different times. (60 significantly PI3K‐p85, p‐Akt, p‐AS160, membrane‐bound cyclin D1, had almost no effect on total protein. Furthermore, declined uptake retarded D1‐mediated cell cycle arrest phase. This study demonstrated inhibit development may be due inhibiting PI3K/Akt/AS160/GLUT1 signalling pathway regulate proliferation cycle, supporting as a potential therapeutic drug for

Язык: Английский

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LncRNA MALAT1 Aggravates Renal Tubular Injury via Activating LIN28A and the Nox4/AMPK/mTOR Signaling Axis in Diabetic Nephropathy

Frontiers in Endocrinology, Год журнала: 2022, Номер 13

Опубликована: Июнь 23, 2022

Background Diabetic nephropathy (DN) is a serious complication among patients with diabetes. Elucidating its pathogenesis crucial for identifying novel biomarkers and therapeutic targets DN. Methods DN tissues were harvested examining MALAT1, LIN28A Nox4. Human kidney-2 (HK-2) cells treated high glucose (HG) establishing cell model of Cell viability was examined by MTT assay. HG-induced apoptosis secretion TNF-α IL-6 analyzed TUNEL ELISA assays, respectively. RIP RNA pull-down assays applied to analyze the interaction between Nox4 in HK-2 human embryonic kidney 293T (HEK-293T) cells. A rat established determine role MALAT1 vivo . Results upregulated HG-treated Overexpression or reduced enhanced apoptosis, ROS generation inflammatory cytokines cells, whereas knockdown exerted opposite effects. Furthermore, directly interacted LIN28A. Moreover, facilitated increase stability. Knockdown relieved injury suppressing AMPK/mTOR signaling alleviated renal tubular epithelial Nox4/AMPK/TOR Conclusion activates via interacting stabilize mRNA, thereby aggravating glucose-induced injury. Our findings provide potential

Язык: Английский

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Sestrin2 attenuates renal damage by regulating Hippo pathway in diabetic nephropathy

Cell and Tissue Research, Год журнала: 2022, Номер 390(1), С. 93 - 112

Опубликована: Июль 12, 2022

Язык: Английский

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Epigenetic modification in diabetic kidney disease

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Июнь 30, 2023

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death patients. The manifestations DKD are proteinuria decreased renal filtration capacity. glomerular rate urinary albumin level two most important hallmarks progression DKD. classical treatment controlling blood glucose pressure. However, commonly used clinical therapeutic strategies existing biomarkers only partially slow roughly predict progression. Therefore, novel methods, targets urgently needed to meet requirements. In recent years, increasing attention has been given role epigenetic modification pathogenesis Epigenetic variation mainly includes DNA methylation, histone changes noncoding RNA expression profile, which deeply involved DKD-related inflammation, oxidative stress, hemodynamics, activation abnormal signaling pathways. Since reversible at certain stages, it valuable identify modifications as early diagnosis prevent end-stage (ESRD). Because current understanding mechanism not comprehensive, purpose this review summarize occurrence development evaluate value therapies

Язык: Английский

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LncRNA H19: a novel player in the regulation of diabetic kidney disease

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Окт. 27, 2023

Diabetic kidney disease (DKD), one of the most severe complications diabetes mellitus (DM), has received considerable attention owing to its increasing prevalence and contribution chronic (CKD) end-stage (ESRD). However, use drugs targeting DKD remains limited. Recent data suggest that long non-coding RNAs (lncRNAs) play a vital role in development DKD. The lncRNA H19 is first imprinted gene, which expressed embryo down-regulated at birth, tumors been subject controversy, however, recent years, it disease. LncRNA engaged pathological progression DKD, including glomerulosclerosis tubulointerstitial fibrosis via induction inflammatory responses, apoptosis, ferroptosis, pyroptosis, autophagy, oxidative damage. In this review, we highlight research on molecular mechanism regulatory forms epigenetic, post-transcriptional, post-translational regulation, providing new predictive marker therapeutic target for management

Язык: Английский

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Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Июнь 9, 2023

Diabetic nephropathy (DN) is a serious microvascular complication of diabetes. It has become leading cause death in patients with diabetes and end-stage renal disease. Ferroptosis newly discovered pattern programmed cell death. Its main manifestation the excessive accumulation intracellular iron ion-dependent lipid peroxides. Recent studies have shown that ferroptosis an important driving factor onset development DN. closely associated intrinsic (including tubular epithelial cells, podocytes, mesangial cells) damage Chinese herbal medicine widely used treatment DN, long history definite curative effect. Accumulating evidence suggests can modulate cells show great potential for improving In this review, we outline key regulators pathways DN summarize herbs, mainly monomers extracts, target inhibition ferroptosis.

Язык: Английский

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RMRP accelerates ligamentum flavum hypertrophy by regulating GSDMD-mediated pyroptosis through Gli1 SUMOylation

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Авг. 16, 2024

Hypertrophy of ligamentum flavum (LF) is a significant contributing factor to lumbar spinal canal stenosis (LSCS). lncRNA plays vital role in organ fibrosis, but its LF fibrosis remains unclear. Our previous findings have demonstrated that Hedgehog-Gli1 signaling critical driver leading hypertrophy. Through the RIP experiment, our group found lnc-RMRP was physically associated with Gli1 and exhibited enrichment Gli1-activated cells. Histological studies revealed elevated expression RMRP hypertrophic LF. In vitro experiments further confirmed promoted SUMO modification nucleus transfer. Mechanistically, induced GSDMD-mediated pyroptosis, proinflammatory activation, collagen through Hedgehog pathway. Notably, mechanical stress-induced hypertrophy rabbit analogous pathological changes occurred human showed enhanced levels α-SMA. Knockdown resulted decreased pyroptosis-related proteins, ultimately ameliorating fibrosis. The above data concluded exerts crucial regulating pyroptosis cells via SUMOylation, thus indicating targeting could serve as potential effective therapeutic strategy for

Язык: Английский

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Roxadustat regulates the cell cycle and inhibits proliferation of mesangial cells via the hypoxia-inducible factor-1α/P53/P21 pathway

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 18, 2025

Over-proliferation of mesangial cells (MCs) is one the main pathological changes in early stages diabetic kidney disease (DKD). Roxadustat, an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, widely studied different models disease. Whether roxadustat has beneficial effect on proliferation MCs and DKD remains unknown. The optimal concentration for inhibiting MC was determined using CCK-8 colony formation assays. Changes cell cycle were detected flow cytometry, cycle-related proteins screened quantitative reverse transcription polymerase chain reaction. Reverse experiments applied Trp53-/- line. Co-immunoprecipitation used to verify interaction between HIF-1α p53 predict sites interaction. Finally, a corresponding vivo verification performed. Optimal concentrations high glucose (30 mM) (100 μM) established. Roxadustat showed anti-proliferation through S-phase arrest. HIF-1α/p53/p21 downstream cyclins (cyclin A1, cyclin A2, E1) changes. A experiment confirmed that affected p53, co-immunoprecipitation results p53. Molecular docking predicted possible Lys328, Pro332, Arg245, Lys251 Ala222, Tyr226, Glu225, Asp265 respectively. animal demonstrated similar db/db mice. regulates inhibits via pathway. This may be potential therapeutic target

Язык: Английский

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Extracellular vesicles derived from mesenchymal stem cells alleviate renal fibrosis via the miR-99b-5p/mTOR/autophagy axis in diabetic kidney disease

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Март 18, 2025

Diabetic kidney disease (DKD) is the leading cause of end-stage renal (ESRD) globally, presenting a significant therapeutic challenge. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) have emerged as promising agents. This study explored effects and mechanisms EVs derived human placental (hP-MSCs) on DKD. were isolated cultured hP-MSCs administered to streptozotocin (STZ)-induced diabetic mice high glucose–treated glomerular mesangial cells. The impact was assessed through histological analysis biochemical assays. miR-99b-5p expression in its role modulating mechanistic target rapamycin (mTOR)/autophagy pathway examined via western blotting RT‒qPCR. Treatment with hP-MSC-derived significantly alleviated fibrosis improved function DKD models. These enriched miR-99b-5p, which targeted inhibited mTOR signaling, thereby increasing autophagic activity reducing cellular proliferation extracellular matrix accumulation tissues. can mitigate injury by miR-99b-5p/mTOR/autophagy pathway. findings suggest potential cell-free strategy for managing

Язык: Английский

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