Elevation of JAML Promotes Diabetic Kidney Disease by Modulating Podocyte Lipid Metabolism

Yi, Fujin; Sun, Yu; Wang, Mei; Hou, Yingyong; Huang, Wei; Zhou, Di; Wang, Ziying; Yang, Song; Tang, Wei; Zhen, Junhui; Li, Yujia; Wang, Xiaojie; Liu, Min; Zhang, Yan; Wang, Baobao; Liu, Guangyi; Yu, Xiao; Sun, Junying; Zhang, Chun; Yi, Fan

doi:10.1016/j.cmet.2020.10.019

Cited by 85 publications

(71 citation statements)

References 44 publications

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“…The pathological processes that drive podocyte dysfunction involve sirtuin 1 (SIRT1), a deacetylase that regulates cell inflammation, apoptosis, proliferation, autophagy, energy metabolism, and oxidative stress [13]. SIRT1 appears to exert a renoprotective effect in kidney diseases, including DN [14][15][16]. 3,5-Diiodothyronine can inhibit mesangial cell proliferation and decrease proteinuria by activating SIRT1 in rat mesangial cells [17].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of miRNA-155 Alleviates High Glucose-Induced Podocyte Inflammation by Targeting SIRT1 in Diabetic Mice

Wang

Gao

et al. 2021

Journal of Diabetes Research

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Objective. Microinflammation plays a crucial role in podocyte dysfunction in diabetic nephropathy, but its regulatory mechanism is still unclear. This study is aimed at discussing the mechanisms underlying the effect of miRNA-155 on podocyte injury to determine its potential as a therapeutic target. Methods. Cultured immortalized mouse podocytes and diabetic KK-Ay mice models were treated with a miR-155 inhibitor. Western blotting, real-time PCR, ELISA, immunofluorescence, and Luciferase reporter assay were used to analyze markers of inflammation cytokines and podocyte injury. Results. miRNA-155 was found to be highly expressed in serum and kidney tissue of mice with diabetic nephropathy and in cultured podocytes, accompanied by elevated levels of inflammatory factors. Inhibition of miRNA-155 can reduce proteinuria and ACR levels, diminish the secretion of inflammatory molecules, improve kidney function, inhibit podocyte foot fusion, and reverse renal pathological changes in diabetic nephropathy mice. Overexpression of miRNA-155 in vitro can increase inflammatory molecule production in podocytes and aggravates podocyte injury, while miRNA-155 inhibition suppresses inflammatory molecule production in podocytes and reduces podocyte injury. A luciferase assay confirmed that miRNA-155 could selectively bind to 3 ′ -UTR of SIRT1, resulting in decreased SIRT1 expression. In addition, SIRT1 siRNA could offset SIRT1 upregulation and enhance inflammatory factor secretion in podocytes, induced by the miRNA-155 inhibitor. Conclusions. These findings strongly support the hypothesis that miRNA-155 inhibits podocyte inflammation and reduces podocyte injury through SIRT1 silencing. miRNA-155 suppression therapy may be useful for the management of diabetic nephropathy.

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Section: Introductionmentioning

confidence: 99%

Inhibition of miRNA-155 Alleviates High Glucose-Induced Podocyte Inflammation by Targeting SIRT1 in Diabetic Mice

Wang

Gao

et al. 2021

Journal of Diabetes Research

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“…Podocyte specific deletion of JAML alleviates pathologies related to diabetic kidney disease such as lowering renal lipotoxicity impairing the progress of the disease. [154] VEGF-B also emerges as a critical target that elevates glomerular lipid content and causes insulin resistance in podocytes. Inhibition of VEGF-B via pharmacological or genetic approaches ameliorates diabetic kidney disease in type 2 diabetes mouse models.…”

Section: Diabetic Kidney Diseasementioning

confidence: 99%

“…Podocyte specific deletion of JAML alleviates pathologies related to diabetic kidney disease such as lowering renal lipotoxicity impairing the progress of the disease. [ 154 ]…”

Section: Diabetic Complicationsmentioning

confidence: 99%

Emerging Targets in Type 2 Diabetes and Diabetic Complications

et al. 2021

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Type 2 diabetes is a metabolic, chronic disorder characterized by insulin resistance and elevated blood glucose levels. Although a large drug portfolio exists to keep the blood glucose levels under control, these medications are not without side effects. More importantly, once diagnosed diabetes is rarely reversible. Dysfunctions in the kidney, retina, cardiovascular system, neurons, and liver represent the common complications of diabetes, which again lack effective therapies that can reverse organ injury. Overall, the molecular mechanisms of how type 2 diabetes develops and leads to irreparable organ damage remain elusive. This review particularly focuses on novel targets that may play role in pathogenesis of type 2 diabetes. Further research on these targets may eventually pave the way to novel therapies for the treatment-or even the prevention-of type 2 diabetes along with its complications.

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“…Podocytes are located on the surface of glomerular capillaries. They are highly differentiated epithelial cells that work with endothelium to maintain normal glomerular filtration function ( 154 ). Podocyte damage is a hallmark pathological manifestation of early DKD.…”

Section: Microvesselsmentioning

confidence: 99%

Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

Chen

Wang

et al. 2021

Front. Endocrinol.

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Diabetic vascular complications (DVC) including macrovascular and microvascular lesions, have a significant impact on public health, and lead to increased patient mortality. Disordered intercellular cascades play a vital role in diabetic systemic vasculopathy. Exosomes participate in the abnormal signal transduction of local vascular cells and mediate the transmission of metabolic disorder signal molecules in distant organs and cells through the blood circulation. They can store different signaling molecules in the membrane structure and release them into the blood, urine, and tears. In recent years, the carrier value and therapeutic effect of exosomes derived from stem cells have garnered attention. Exosomes are not only a promising biomarker but also a potential target and tool for the treatment of DVC. This review explored changes in the production process of exosomes in the diabetic microenvironment and exosomes’ early warning role in DVC from different systems and their pathological processes. On the basis of these findings, we discussed the future direction of exosomes in the treatment of DVC, and the current limitations of exosomes in DVC research.

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Elevation of JAML Promotes Diabetic Kidney Disease by Modulating Podocyte Lipid Metabolism

Cited by 85 publications

References 44 publications

Inhibition of miRNA-155 Alleviates High Glucose-Induced Podocyte Inflammation by Targeting SIRT1 in Diabetic Mice

Inhibition of miRNA-155 Alleviates High Glucose-Induced Podocyte Inflammation by Targeting SIRT1 in Diabetic Mice

Emerging Targets in Type 2 Diabetes and Diabetic Complications

Exosomes: Biomarkers and Therapeutic Targets of Diabetic Vascular Complications

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