Proteomic and microRNA‑omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation

Ding, Yipei; Zhong, Jin; Wang, Yangyang; Xie, Weidong

doi:10.3892/etm.2020.9554

Cited by 4 publications

(4 citation statements)

References 40 publications

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“…For the purpose of targeted treatment of type 2 diabetes, the specific mechanism of the occurrence and development of type 2 diabetes shall be firstly clarified. A high-glucose state can be found in diabetic patients, and long-term hyperglycemia will cause direct damage to islet B cells, promote the apoptosis of islet B cells, and inhibit their activity [4,18]. Impaired islet B cell activity will further aggravate insulin resistance in patients and eventually lead to the reduction of insulin release and further improvement of blood glucose, forming a vicious circle [19].…”

Section: Discussionmentioning

confidence: 99%

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hMSCs Migrate under the Chemotaxis of CXCL-13 and Enhance Islet B Cell Activity through p-AKT Signaling Pathway in High-Glucose Environment

Bian

Jiang

et al. 2022

Journal of Healthcare Engineering

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As a common clinical chronic disease, the incidence of diabetes is increasing year by year. According to the latest statistics from the International Diabetes Federation, as of 2019, the global prevalence of diabetes has reached 8.3%. This study aims to investigate the effect of CXCL-13 on the migration ability of human mesenchymal stem cells (hMSCs) and to clarify the specific molecular mechanism of the protective effect of hMSCs on islet B cells. The hMSCs were cultured in high-glucose environment, and the effect of CXCL-13 on the migration ability of hMSCs was determined by Transwell experiment. After coculture of hMSCs and islet B cells, the activity of cells was detected by CCK8 assay, the expression of Ki-67 in cells was detected by RT-PCR, and the expression of P53 was detected by Western blot to investigate the effect of hMSCs on the proliferation and apoptosis of islet B cells. The effect of hMSCs on the function of islet B cells was determined by glucose stimulated insulin secretion experiment. Transwell experiment results showed that CXCL-13 could promote the migration of hMSCs to islet B cells in high-glucose environment. The results of CCK-8 showed that the cell activity in the coculture group was significantly higher than that of the other groups, and RT-PCR showed that the expression of Ki-67 was significantly increased in the coculture group of hMSCs and islet B cells. The results of Western blot showed that the expression of P53 was significantly decreased in the coculture group, and the glucose stimulated insulin secretion test showed that insulin secretion was significantly increased. It was found that after the inhibition of ATK, cell activity was significantly reduced, and apoptosis was significantly increased. Meanwhile, the expression of Ki-67 was inhibited, the expression of P-53 was significantly increased, and insulin secretion was significantly reduced. To sum up, in a high-glucose environment, CXCL-13 effectively promoted the migration of hMSCs, and hMSCs protected the activity and function of islet B cells through Akt signaling pathway.

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Section: Discussionmentioning

confidence: 99%

“…e mechanism of the development of type 2 diabetes is that long-term chronic hyperglycemia significantly inhibits the activity of islet B cells and promotes the apoptosis of islet B cells [2,3]. e decrease in islet B cells number leads to decreased function of islet B cells [4].…”

Section: Introductionmentioning

confidence: 99%

hMSCs Migrate under the Chemotaxis of CXCL-13 and Enhance Islet B Cell Activity through p-AKT Signaling Pathway in High-Glucose Environment

Bian

Jiang

et al. 2022

Journal of Healthcare Engineering

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“…BAY-117082 is an NF-κB pathway inhibitor that can inhibit p65 nuclear translocation and DNA binding activity [ 23 ]. According to previous research [ 24 ], we treated cells with 10 µM BAY-117082 (Med Chem Express) at 37 ℃ for 1 h to inhibit NF-κB pathway. Compared with the CX3CL1 group, the level of iNOS was significantly decreased in the CX3CL1+ BAY-117082 group (Fig.…”

Section: Resultsmentioning

confidence: 99%

CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro

Feng,

Zhu,

Qiao

et al. 2023

J Transl Med

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Background Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice. Methods The authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage. Results The authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation. Conclusions The study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment.

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“…Indeed, under systemic inflammatory conditions, pro-inflammatory cytokine TNFα promotes intracellular accumulation of miR-223 in preadipocytes, which in turn impairs their differentiation [41]. Upregulation of miR-146a-5p and miR-21a-5p has been demonstrated in pancreatic islets under inflammatory conditions, and may affect the expression of islet-specific transcription factors, contributing to islet dysfunction [42].…”

Section: Introductionmentioning

confidence: 99%

Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study

Formichi

Fignani

Nigi

et al. 2021

IJMS

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Type 2 diabetes (T2D) represents one of the major health issues of this century. Despite the availability of an increasing number of anti-hyperglycemic drugs, a significant proportion of patients are inadequately controlled, thus highlighting the need for novel biomarkers to guide treatment selection. MicroRNAs (miRNAs) are small non-coding RNAs, proposed as useful diagnostic/prognostic markers. The aim of our study was to identify a miRNA signature occurring in responders to glucagon-like peptide 1 receptor agonists (GLP1-RA) therapy. We investigated the expression profile of eight T2D-associated circulating miRNAs in 26 prospectively evaluated diabetic patients in whom GLP1-RA was added to metformin. As expected, GLP1-RA treatment induced significant reductions of HbA1c and body weight, both after 6 and 12 months of therapy. Of note, baseline expression levels of the selected miRNAs revealed two distinct patient clusters: “high expressing” and “low expressing”. Interestingly, a significantly higher percentage of patients in the high expression group reached the glycemic target after 12 months of treatment. Our findings suggest that the evaluation of miRNA expression could be used to predict the likelihood of an early treatment response to GLP1-RA and to select patients in whom to start such treatment, paving the way to a personalized medicine approach.

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Proteomic and microRNA‑omic profiles and potential mechanisms of dysfunction in pancreatic islet cells primed by inflammation

Cited by 4 publications

References 40 publications

hMSCs Migrate under the Chemotaxis of CXCL-13 and Enhance Islet B Cell Activity through p-AKT Signaling Pathway in High-Glucose Environment

hMSCs Migrate under the Chemotaxis of CXCL-13 and Enhance Islet B Cell Activity through p-AKT Signaling Pathway in High-Glucose Environment

CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro

Circulating microRNAs Signature for Predicting Response to GLP1-RA Therapy in Type 2 Diabetic Patients: A Pilot Study

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