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

Song, Panai; Chen, Yinyin; Liu, Zhiwen; Liu, Hong; Xiao, Li; Sun, Lin; Wei, Jiali; He, Liyu

doi:10.3389/fendo.2022.895360

Cited by 11 publications

(9 citation statements)

References 41 publications

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“…In the current study, INO treatment signi cantly inhibited ROS levels reduced NOX4 expression. Similarly, Song et al demonstrated that ROS can accelerate the disease development of DN by treating human kidney-2 (HK-2) cells with HG to establish a cellular model of DN, knocking down NOX4 intracellularly and alleviating HG-induced cell damage by inhibiting AMPK/mTOR signaling in HK-2 cells 25 . Nrf2 is a key transcription factor that regulates oxidative stress and is capable of regulating both oxidative stress damage in type 2 DN 26,27 .…”

Section: Discussionmentioning

confidence: 99%

Inotodiol Ameliorates Oxidative Stress and Apoptosis by Regulating PI3K/Akt/GSK-3β Signaling Pathways in Diabetic Nephropathy

Tian,

Duan,

et al. 2024

Preprint

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Diabetic nephropathy (DN), a kind of microvascular complication, is a primary cause of end-stage kidney disease worldwide. However, therapeutic drugs for DN treatment are still in lack. Inotodiol (INO), a kind of lanostane triterpenoid isolated from INO that has various biological activities. In this study, we employed db/db mice as the spontaneous DN model in vivo, and high glucose treated MPC5 cells in vitro to elucidate the protective effects and underlying mechanisms of INO in DN. Ratio of right kidney weight/body weight was calculated, and levels of FBG, urine albumin/creatinine (UACR), BUN and Scr were measured. The SOD, CAT, GSH-Px and MDA levels in kidney were detected by using commercial kits. The histopathological changes of renal tissues were assessed by HE, PAS and Masson staining. The intracellular ROS was detected by using fluorescence probe DCHF-DA. Cytotoxicity assay was performed using CCK-8 assay kit. The rate of apoptosis was detected by flow cytometry. The expressions of Bax, Bcl-2, Cytc, Cleaved caspase-3, GSK-3β, pSer-GSK-3β, Akt, p-Akt, Synaptopodin, WT-1, Nrf2, NQO1, Keap1, heme HO-1 were measured by western blot. The expressions of Bax, CytC, WT-1, Synaptopodin, Bcl-2, GSK-3β and pSer9-GSK-3β in renal tissues were measured by immunohistochemistry. Our results showed that INO treatment reduced the FBG, BUN, Scr and UACR levels in db/db mice. Moreover, INO increased the expressions of Synaptopodin and WT-1 proteins. Besides, INO treatment also mitigated kidney histopathological changes, reduces kidney oxidative stress as reflected by reduced levels of Keap-1, NOX4 and MDA, but increased levels of kidney antioxidants SOD, CAT, GSH-Px, Nrf2, NQO1 and HO-1. Additionally, kidney apoptosis decreased as reflected by decreased protein levels of Cytc, Bax and Cleaved caspase-3 while its anti-apoptosis Bcl-2 protein levels increased. Mechanistically, INO inhibited GSK-3β activity by activating the PI3K/Akt signaling pathway, increased the level of anti-apoptosis, decreased level of oxidative stress and reduced podocyte injury in vivo and in vitro. Collectively, these results indicated that INO protected against DN through ameliorating oxidative stress and apoptosis via the PI3K/Akt/GSK-3β pathway.

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Section: Discussionmentioning

confidence: 99%

Inotodiol Ameliorates Oxidative Stress and Apoptosis by Regulating PI3K/Akt/GSK-3β Signaling Pathways in Diabetic Nephropathy

Tian,

Duan,

et al. 2024

Preprint

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“…These actions would allow MALAT1 to exacerbate high glucose-induced renal tubular epithelial injury. 263 ZNF503-AS1 is a novel lncRNA with higher expression in patients with DR than in control patients. By activating TGF-β signalling, ZNF503-AS1 overexpression promotes apoptosis and suppresses proliferation.…”

Section: The Role Of Mirnas In Metabolic Diseasementioning

confidence: 99%

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

Lin

et al. 2023

Sig Transduct Target Ther

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Epigenetics regulates gene expression and has been confirmed to play a critical role in a variety of metabolic diseases, such as diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), osteoporosis, gout, hyperthyroidism, hypothyroidism and others. The term ‘epigenetics’ was firstly proposed in 1942 and with the development of technologies, the exploration of epigenetics has made great progresses. There are four main epigenetic mechanisms, including DNA methylation, histone modification, chromatin remodelling, and noncoding RNA (ncRNA), which exert different effects on metabolic diseases. Genetic and non-genetic factors, including ageing, diet, and exercise, interact with epigenetics and jointly affect the formation of a phenotype. Understanding epigenetics could be applied to diagnosing and treating metabolic diseases in the clinic, including epigenetic biomarkers, epigenetic drugs, and epigenetic editing. In this review, we introduce the brief history of epigenetics as well as the milestone events since the proposal of the term ‘epigenetics’. Moreover, we summarise the research methods of epigenetics and introduce four main general mechanisms of epigenetic modulation. Furthermore, we summarise epigenetic mechanisms in metabolic diseases and introduce the interaction between epigenetics and genetic or non-genetic factors. Finally, we introduce the clinical trials and applications of epigenetics in metabolic diseases.

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“…MALAT1 activated LIN28 and Nox4/AMPK/mTOR pathway, resulting in promotion of renal tubular injury in diabetic nephropathy (41). Huang et al reported that MALAT1 aggravated renal fibrosis via modulation of miR-2355-3p/IL6ST axis in diabetic nephropathy (42).…”

Section: Lncrna Malat1mentioning

confidence: 99%

“…MALAT1 activated LIN28 and Nox4/AMPK/mTOR pathway, resulting in promotion of renal tubular injury in diabetic nephropathy ( 41 ). Huang et al.…”

Section: Role Of Lncrnas In Dkdmentioning

confidence: 99%

The role of lncRNAs in regulation of DKD and diabetes-related cancer

Cheng

Xia

et al. 2022

Front. Oncol.

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Diabetes mellitus often results in several complications, such as diabetic kidney disease (DKD) and end-stage renal diseases (ESRDs). Cancer patients often have the dysregulated glucose metabolism. Abnormal glucose metabolism can enhance the tumor malignant progression. Recently, lncRNAs have been reported to regulate the key proteins and signaling pathways in DKD development and progression and in cancer patients with diabetes. In this review article, we elaborate the evidence to support the function of lncRNAs in development of DKD and diabetes-associated cancer. Moreover, we envisage that lncRNAs could be diagnosis and prognosis biomarkers for DKD and cancer patients with diabetes. Furthermore, we delineated that targeting lncRNAs might be an alternative approach for treating DKD and cancer with dysregulated glucose metabolism.

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

Cited by 11 publications

References 41 publications

Inotodiol Ameliorates Oxidative Stress and Apoptosis by Regulating PI3K/Akt/GSK-3β Signaling Pathways in Diabetic Nephropathy

Inotodiol Ameliorates Oxidative Stress and Apoptosis by Regulating PI3K/Akt/GSK-3β Signaling Pathways in Diabetic Nephropathy

Epigenetic regulation in metabolic diseases: mechanisms and advances in clinical study

The role of lncRNAs in regulation of DKD and diabetes-related cancer

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