Long Non-Coding RNAs in the Pathogenesis of Diabetic Kidney Disease DOI Creative Commons

Mengsi Hu,

Qiqi Ma, Bing Liu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 20, 2022

Diabetic kidney disease (DKD) is one of the major microvascular complications diabetes mellitus, with relatively high morbidity and mortality globally but still in short therapeutic options. Over decades, a large body data has demonstrated that oxidative stress, inflammatory responses, hemodynamic disorders might exert critical influence initiation development DKD, whereas delicate pathogenesis DKD remains profoundly elusive. Recently, long non-coding RNAs (lncRNAs), extensively studied field cancer, are attracting increasing attentions on mellitus its including diabetic retinopathy, cardiomyopathy. In this review, we chiefly focused abnormal expression function lncRNAs resident cells (mesangial cell, endothelial podocyte, tubular epithelial cell) kidney, summarized roles elaborated their potential significance, order to advance our knowledge field, which help future research clinical treatment for disease.

Language: Английский

Berberine regulates mesangial cell proliferation and cell cycle to attenuate diabetic nephropathy through the PI3K/Akt/AS160/GLUT1 signalling pathway DOI
Wei‐Jian Ni,

Ximei Guan,

Jing Zeng

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2022, Volume and Issue: 26(4), P. 1144 - 1155

Published: Jan. 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

Language: Английский

Citations

21
Artesunate Alleviates Kidney Fibrosis in Type 1 Diabetes with Periodontitis Rats via Promoting Autophagy and Suppression of Inflammation DOI Creative Commons
Chen Liang,

MA Licheng,

Yi Chen

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 9(14), P. 16358 - 16373

Published: March 29, 2024

To explore the effect of periodontal disease on progression diabetic kidney (DKD), to observe effects artesunate (ART) intervention and tissues in type 1 rats with periodontitis, possibility ART for treatment DKD. Rat models diabetes mellitus, mellitus periodontitis were established through streptozotocin (STZ) intraperitoneal injection, maxillary first molar ligation, P. gingivalis ligation applied sequentially. Ten weeks after modeling, gavage was given 4 weeks. Immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot used investigate inflammatory factors, fibrogenisis, autophagy-related proteins tissues, 16S rDNA sequencing detect changes dental plaque fluid tissue flora. Compared control group, protein expression levels transforming growth factor β1 (TGF-β1) COL-IV (PD) group increased. The TGF-β1, Smad3, increased DM + PD upregulated group. These results suggest that enhances renal fibrosis this process is related TGF-β1/Smad/COL-IV signaling pathway. Among top five dominant bacteria abundance Proteobacteria most significantly, followed by Actinobacteria Firmicutes mild increases. relative Proteobacteria, Actinobacteria, groups also showed an increasing trend compared CON trend, which may mediate increase oxidative stress promote occurrence development DN. Periodontal lead imbalance flora, aggravate damage T1DM, cause glomerular inflammation tubulointerstitial fibrosis, reduce level autophagy. delays inhibiting TGF-β-Smad

Language: Английский

Citations

4
LncRNA MALAT1 Aggravates Renal Tubular Injury via Activating LIN28A and the Nox4/AMPK/mTOR Signaling Axis in Diabetic Nephropathy DOI Creative Commons

Panai Song,

Yinyin Chen, Zhiwen Liu

et al.

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

Published: June 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

Language: Английский

Citations

18
Epigenetic modification in diabetic kidney disease DOI Creative Commons
Zhe Liu, Jiahui Liu,

Wanning Wang

et al.

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

Published: June 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

Language: Английский

Citations

11
LncRNA H19: a novel player in the regulation of diabetic kidney disease DOI Creative Commons
Qinrui Wu, Fengjuan Huang

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

Published: Oct. 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

Language: Английский

Citations

11
Ferroptosis: a new strategy for Chinese herbal medicine treatment of diabetic nephropathy DOI Creative Commons

Maoying Wei,

Xingxing Liu,

Zhijuan Tan

et al.

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

Published: June 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.

Language: Английский

Citations

10
Roxadustat regulates the cell cycle and inhibits proliferation of mesangial cells via the hypoxia-inducible factor-1α/P53/P21 pathway DOI Creative Commons
Yun Cheng, Qingmei Yang,

Baijie Feng

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 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

Language: Английский

Citations

0
Extracellular vesicles derived from mesenchymal stem cells alleviate renal fibrosis via the miR-99b-5p/mTOR/autophagy axis in diabetic kidney disease DOI Creative Commons
Rongrong Li,

Hongyan Tao,

Kai Pan

et al.

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 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

Language: Английский

Citations

0
Trim33 inhibited the growth and relieved the fibrosis of mesangial cells through inducing the ubiquitination degradation of Smad2 DOI
Zhiyuan Liu, Yong Zhang, Hongzhou Li

et al.

Tissue and Cell, Journal Year: 2025, Volume and Issue: 95, P. 102915 - 102915

Published: April 11, 2025

Language: Английский

Citations

0
Rs9839776 Genetic Variant of lncRNA SOX2OT Contributes to Susceptibility of Acute Kidney Injury in Sepsis Patients via Regulating SOX2OT/miR-9-5p Axis DOI Creative Commons

Shuying Xu,

Mingli Cui,

Ruixia Wang

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 6077 - 6089

Published: May 1, 2025

Single nucleotide polymorphisms (SNPs) are commonly found in lncRNA, and can regulate its expression. The study examined the genotype allele distributions of rs9839776 polymorphism lncRNA SOX2OT sepsis patients with acute kidney injury (AKI), as well expression changes. function AKI cell model was also elucidated. Serum levels were via qRT-PCR 450 septic including 202 cases 248 without. Genotyping completed Taqman real-time PCR. HK-2 cells treated LPS to mimic AKI, viability, apoptosis inflammatory response evaluated after regulating levels. pathways enriched by downstream target genes explored GO KEGG analysis. Rs9839776 CC carriers observed presented reduced SOX2OT. lowly expressed patients, which distinguish from ones. In vitro, alleviated LPS-induced mediating proliferation, response, reversed miR-9-5p. analysis uncovered significant links miR-9-5p cytoskeleton muscle cells, adhesion molecules prolactin signaling pathway. could affect susceptibility for its-mediated downregulation may serve a biomarker AKI. underlying mechanism might be related mediation SOX2OT/miR-9-5p axis.

Language: Английский

Citations

0