Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury
Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard g...
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MDPI AG
2024-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/13/23/2021 |
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| author | Khandaker N. Anwar Mohammad Soleimani Mohammad Javad Ashraf Amirhossein Moghtader Raghuram Koganti Seyyedehfatemeh Ghalibafan Mahbod Baharnoori Zohreh Arabpour Kasra Cheraqpour Aron M. Sebhat Mansour Abtahi Xincheng Yao Mahmood Ghassemi Ali R. Djalilian |
| author_facet | Khandaker N. Anwar Mohammad Soleimani Mohammad Javad Ashraf Amirhossein Moghtader Raghuram Koganti Seyyedehfatemeh Ghalibafan Mahbod Baharnoori Zohreh Arabpour Kasra Cheraqpour Aron M. Sebhat Mansour Abtahi Xincheng Yao Mahmood Ghassemi Ali R. Djalilian |
| author_sort | Khandaker N. Anwar |
| collection | DOAJ |
| description | Mustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study aimed to assess senescence and stress-related pathways—particularly mitogen-activated protein kinase (MAPK) signaling—in nitrogen mustard (NM)-induced corneal injury. In vitro, primary human corneal epithelial (P-HCECs), primary human corneal mesenchymal stromal cells (hcMSCs), and human corneal–limbal epithelial cell (HCLE) lines were exposed to varying concentrations of NM. The results demonstrated a dose-dependent increase in cellular senescence, characterized by reduced Ki67 expression, elevated p16, and p21 mRNA levels, as well as activation of the MAPK pathway activation. Treatment with a selective p38-MAPK inhibitor significantly reduced senescence markers and improved cell proliferation following exposure to NM. Overall, these studies indicate that NM exposure triggers cellular senescence and stress-related MAPK signaling, while p38-MAPK inhibition mitigates these effects, suggesting a potential therapeutic strategy. |
| format | Article |
| id | doaj-art-62228c8d6aee4dfb86196a99d06f48a2 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-62228c8d6aee4dfb86196a99d06f48a22024-12-13T16:24:20ZengMDPI AGCells2073-44092024-12-011323202110.3390/cells13232021Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard InjuryKhandaker N. Anwar0Mohammad Soleimani1Mohammad Javad Ashraf2Amirhossein Moghtader3Raghuram Koganti4Seyyedehfatemeh Ghalibafan5Mahbod Baharnoori6Zohreh Arabpour7Kasra Cheraqpour8Aron M. Sebhat9Mansour Abtahi10Xincheng Yao11Mahmood Ghassemi12Ali R. Djalilian13Department of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Biomedical Engineering, University of Illinois Chicago, Chicago, IL 60607, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USADepartment of Ophthalmology and Visual Sciences, University of Illinois Chicago, Chicago, IL 60612, USAMustard gas keratopathy (MGK), a complication of exposure to sulfur mustard, is a blinding ocular surface disease involving key cellular pathways, including apoptosis, oxidative stress, and inflammation. Recent studies indicate that cellular senescence contributes to the pathophysiology of mustard gas toxicity. This study aimed to assess senescence and stress-related pathways—particularly mitogen-activated protein kinase (MAPK) signaling—in nitrogen mustard (NM)-induced corneal injury. In vitro, primary human corneal epithelial (P-HCECs), primary human corneal mesenchymal stromal cells (hcMSCs), and human corneal–limbal epithelial cell (HCLE) lines were exposed to varying concentrations of NM. The results demonstrated a dose-dependent increase in cellular senescence, characterized by reduced Ki67 expression, elevated p16, and p21 mRNA levels, as well as activation of the MAPK pathway activation. Treatment with a selective p38-MAPK inhibitor significantly reduced senescence markers and improved cell proliferation following exposure to NM. Overall, these studies indicate that NM exposure triggers cellular senescence and stress-related MAPK signaling, while p38-MAPK inhibition mitigates these effects, suggesting a potential therapeutic strategy.https://www.mdpi.com/2073-4409/13/23/2021mustardnitrogen mustardmustard keratopathysenescenceMAPKMAPK inhibitor |
| spellingShingle | Khandaker N. Anwar Mohammad Soleimani Mohammad Javad Ashraf Amirhossein Moghtader Raghuram Koganti Seyyedehfatemeh Ghalibafan Mahbod Baharnoori Zohreh Arabpour Kasra Cheraqpour Aron M. Sebhat Mansour Abtahi Xincheng Yao Mahmood Ghassemi Ali R. Djalilian Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury Cells mustard nitrogen mustard mustard keratopathy senescence MAPK MAPK inhibitor |
| title | Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury |
| title_full | Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury |
| title_fullStr | Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury |
| title_full_unstemmed | Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury |
| title_short | Senescence and Stress Signaling Pathways in Corneal Cells After Nitrogen Mustard Injury |
| title_sort | senescence and stress signaling pathways in corneal cells after nitrogen mustard injury |
| topic | mustard nitrogen mustard mustard keratopathy senescence MAPK MAPK inhibitor |
| url | https://www.mdpi.com/2073-4409/13/23/2021 |
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