Metformin mediates MicroRNA-21 regulated circulating matrix metalloproteinase-9 in diabetic nephropathy : an in-silico and clinical study
Metformin is commonly used as an oral hypoglycaemic agent in type 2 diabetes mellitus (T2DM). MicroRNA-21 is widely studied in diabetic and diabetic nephropathy (DN) patients. Matrix metalloproteinase-9 (MMP9) is involved in extracellular matrix degradation and tissue repair processes. However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients. The study subjects were divided into three groups (Healthy controls = 36, T2DM = 38, DN = 35). Anthropometric measurements were taken and biochemical tests were carried out on fasting blood samples. Reverse transcriptase PCR was employed for whole blood gene expression analysis of hsa-miR-21-5p and MMP9. Bioinformatics analyses including drug-gene interaction, protein-protein interaction, functional enrichment analyses and co-expression networks were performed. In the present study, MMP9 and hsa-miR-21-5p levels were downregulated and upregulated respectively in T2DM and DN patients when compared with healthy controls. However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed. In-silico analysis revealed the target genes involved in the miR-21 and MMP9 interaction network. Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:129 |
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| Enthalten in: |
Archives of physiology and biochemistry - 129(2023), 6 vom: 02. Dez., Seite 1200-1210 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Khokhar, Manoj [VerfasserIn] |
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| Links: |
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| Themen: |
9100L32L2N |
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| Anmerkungen: |
Date Completed 16.11.2023 Date Revised 29.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1080/13813455.2021.1922457 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Khokhar, Manoj |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Metformin mediates MicroRNA-21 regulated circulating matrix metalloproteinase-9 in diabetic nephropathy |b an in-silico and clinical study |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Metformin is commonly used as an oral hypoglycaemic agent in type 2 diabetes mellitus (T2DM). MicroRNA-21 is widely studied in diabetic and diabetic nephropathy (DN) patients. Matrix metalloproteinase-9 (MMP9) is involved in extracellular matrix degradation and tissue repair processes. However, the effect of metformin administration on hsa-miR-21-5p and MMP9 has not been evaluated in T2DM and DN patients. The study subjects were divided into three groups (Healthy controls = 36, T2DM = 38, DN = 35). Anthropometric measurements were taken and biochemical tests were carried out on fasting blood samples. Reverse transcriptase PCR was employed for whole blood gene expression analysis of hsa-miR-21-5p and MMP9. Bioinformatics analyses including drug-gene interaction, protein-protein interaction, functional enrichment analyses and co-expression networks were performed. In the present study, MMP9 and hsa-miR-21-5p levels were downregulated and upregulated respectively in T2DM and DN patients when compared with healthy controls. However, in metformin-treated group, a downregulation of hsa-miR-21-5p and upregulation of MMP9 was observed. In-silico analysis revealed the target genes involved in the miR-21 and MMP9 interaction network. Metformin directly targets miR-21 and regulates MMP9 expression in T2DM patients, influencing the pathogenesis of DN.HighlightsMMP-9 and hsa-miR-21-5p were downregulated and upregulated respectively in T2DM and DN patients in a Western Indian population.The patients treated with metformin showed downregulation of hsa-miR-21-5p and upregulation of MMP9.In-silico analysis revealed MMP-9 as well as PTEN to be targets of hsa-miR-21-5p.Metformin regulates MMP9 expression in T2DM and DN patient populations through hsa-miR-21-5p | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Diabetic Nephropathy | |
| 650 | 4 | |a MMP9 | |
| 650 | 4 | |a Metformin | |
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| 700 | 1 | |a Roy, Dipayan |e verfasserin |4 aut | |
| 700 | 1 | |a Bajpai, Nitin Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Bohra, Gopal Krishna |e verfasserin |4 aut | |
| 700 | 1 | |a Yadav, Dharamveer |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Praveen |e verfasserin |4 aut | |
| 700 | 1 | |a Purohit, Purvi |e verfasserin |4 aut | |
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