The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease
Introduction: Klotho and dipeptidyl peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer disease (AD). Methods: This...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Iran University of Medical Sciences
2020-05-01
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| Series: | Basic and Clinical Neuroscience |
| Subjects: | |
| Online Access: | http://bcn.iums.ac.ir/article-1-1459-en.html |
| _version_ | 1797284976733978624 |
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| author | Mohsen Sedighi Tourandokht Baluchnejadmojarad Soudabeh Fallah Nariman Moradi Siamak Afshin-Majd Mehrdad Roghani |
| author_facet | Mohsen Sedighi Tourandokht Baluchnejadmojarad Soudabeh Fallah Nariman Moradi Siamak Afshin-Majd Mehrdad Roghani |
| author_sort | Mohsen Sedighi |
| collection | DOAJ |
| description | Introduction: Klotho and dipeptidyl peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer disease (AD).
Methods: This study was conducted on 16 AD patients and 16 healthy age-matched controls. Plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β, interleukin-6 (IL-6), klotho, and DPP4 were measured by enzyme-linked immunosorbent assay. Plasma expression of miR-29a and miR-195 were also measured and compared by a real-time polymerase chain reaction.
Results: There was a significant increase in TNF-α (p=0.006), IL-1β (p=0.012), and IL-6 (p=0.012) levels in the AD subjects compared with controls. Also, we found a decrease in plasma levels of klotho and an increase in plasma levels of DPP4 in the AD group that was not significant compared with the controls. Lower expression of miR-29a (P=0.009) and higher expression of miR-195 (P=0.003) were observed in the AD group that was significant than controls. Further analysis showed a negative correlation between klotho and plasma levels of IL-6 (r=-0.58, p=0.01). Also, there was a positive correlation between plasma DPP4 activity and TNF-α levels (r=0.50, P=0.04) and IL-1β (r=0.62, P=0.01). Likewise, plasma klotho concentration showed a negative correlation with the age of AD subjects (r=-0.56, P=0.02).
Conclusion: TNF-α, IL-1β, and IL-6 are involved in AD pathophysiology, and dysregulation of DPP4 and klotho may be associated with the inflammatory response of AD. Down-regulation of miR-29a and up-regulation of miR‑195 indicated the role of miRNAs in the AD process. |
| first_indexed | 2024-03-07T17:55:34Z |
| format | Article |
| id | doaj.art-27203b54e9c64c9283555b39b1dbb95c |
| institution | Directory Open Access Journal |
| issn | 2008-126X 2228-7442 |
| language | English |
| last_indexed | 2024-03-07T17:55:34Z |
| publishDate | 2020-05-01 |
| publisher | Iran University of Medical Sciences |
| record_format | Article |
| series | Basic and Clinical Neuroscience |
| spelling | doaj.art-27203b54e9c64c9283555b39b1dbb95c2024-03-02T12:15:54ZengIran University of Medical SciencesBasic and Clinical Neuroscience2008-126X2228-74422020-05-01113349358The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer DiseaseMohsen Sedighi0Tourandokht Baluchnejadmojarad1Soudabeh Fallah2Nariman Moradi3Siamak Afshin-Majd4Mehrdad Roghani5 Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran. Department of Neuroscience, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. Neurophysiology Research Center, Shahed University, Tehran, Iran. Neurophysiology Research Center, Shahed University, Tehran, Iran. Introduction: Klotho and dipeptidyl peptidase-4 (DPP4) are two proteins that modulate inflammatory pathways. We investigated the association between circulating klotho and DPP4 activity and their relationship with inflammatory cytokines, miR-29a, and miR-195 in Alzheimer disease (AD). Methods: This study was conducted on 16 AD patients and 16 healthy age-matched controls. Plasma levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β, interleukin-6 (IL-6), klotho, and DPP4 were measured by enzyme-linked immunosorbent assay. Plasma expression of miR-29a and miR-195 were also measured and compared by a real-time polymerase chain reaction. Results: There was a significant increase in TNF-α (p=0.006), IL-1β (p=0.012), and IL-6 (p=0.012) levels in the AD subjects compared with controls. Also, we found a decrease in plasma levels of klotho and an increase in plasma levels of DPP4 in the AD group that was not significant compared with the controls. Lower expression of miR-29a (P=0.009) and higher expression of miR-195 (P=0.003) were observed in the AD group that was significant than controls. Further analysis showed a negative correlation between klotho and plasma levels of IL-6 (r=-0.58, p=0.01). Also, there was a positive correlation between plasma DPP4 activity and TNF-α levels (r=0.50, P=0.04) and IL-1β (r=0.62, P=0.01). Likewise, plasma klotho concentration showed a negative correlation with the age of AD subjects (r=-0.56, P=0.02). Conclusion: TNF-α, IL-1β, and IL-6 are involved in AD pathophysiology, and dysregulation of DPP4 and klotho may be associated with the inflammatory response of AD. Down-regulation of miR-29a and up-regulation of miR‑195 indicated the role of miRNAs in the AD process.http://bcn.iums.ac.ir/article-1-1459-en.htmlalzheimer disease (ad)klothodipeptidyl peptidase-4inflammatory cytokinesmicrornas |
| spellingShingle | Mohsen Sedighi Tourandokht Baluchnejadmojarad Soudabeh Fallah Nariman Moradi Siamak Afshin-Majd Mehrdad Roghani The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease Basic and Clinical Neuroscience alzheimer disease (ad) klotho dipeptidyl peptidase-4 inflammatory cytokines micrornas |
| title | The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease |
| title_full | The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease |
| title_fullStr | The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease |
| title_full_unstemmed | The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease |
| title_short | The Association Between Circulating Klotho and Dipeptidyl Peptidase-4 Activity and Inflammatory Cytokines in Elderly Patients With Alzheimer Disease |
| title_sort | association between circulating klotho and dipeptidyl peptidase 4 activity and inflammatory cytokines in elderly patients with alzheimer disease |
| topic | alzheimer disease (ad) klotho dipeptidyl peptidase-4 inflammatory cytokines micrornas |
| url | http://bcn.iums.ac.ir/article-1-1459-en.html |
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