ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells
ERK, an extracellular signal-regulated protein kinase, is involved in various biological responses, such as cell proliferation and differentiation, cell morphology maintenance, cytoskeletal construction, apoptosis, and canceration of cells. In this study, we focused on ERK pathway on cellular injury...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2021/6614848 |
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| author | Jian-kun Deng Xueqin Zhang Hong-luan Wu Yu Gan Ling Ye Huijuan Zheng Zebing Zhu Wei Jing Liu Hua-feng Liu |
| author_facet | Jian-kun Deng Xueqin Zhang Hong-luan Wu Yu Gan Ling Ye Huijuan Zheng Zebing Zhu Wei Jing Liu Hua-feng Liu |
| author_sort | Jian-kun Deng |
| collection | DOAJ |
| description | ERK, an extracellular signal-regulated protein kinase, is involved in various biological responses, such as cell proliferation and differentiation, cell morphology maintenance, cytoskeletal construction, apoptosis, and canceration of cells. In this study, we focused on ERK pathway on cellular injury and autophagy-associated adaptive response in urinary protein-irritated renal tubular epithelial cells and explored the potential mechanisms underlying it. By using antioxidants N-acetylcysteine and catalase, we found that ERK pathway was activated by a reactive oxygen species- (ROS-) dependent mechanism after exposure to urinary proteins. What is more, ERK inhibitor U0126 could decrease the release of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and the number of apoptotic cells induced by urinary proteins, indicating the damaging effects of ERK pathway in mediating cellular injury and apoptosis in HK-2 cells. Interestingly, we also found that the increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II (a key marker of autophagy) and the decreased expression of p62 (autophagic substrate) induced by urinary proteins were reversed by U0126, suggesting autophagy was activated by ERK pathway. Furthermore, rapamycin reduced urinary protein-induced NGAL and KIM-1 secretion and cell growth inhibition, while chloroquine played the opposite effect, indicating that autophagy activation by ERK pathway was an adaptive response in the exposure to urinary proteins. Taken together, our results indicate that activated ROS-ERK pathway can induce cellular injury and in the meantime provide an autophagy-associated adaptive response in urinary protein-irritated renal tubular epithelial cells. |
| format | Article |
| id | doaj-art-3c6db3c5a90249739679bcac82a65ab6 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-3c6db3c5a90249739679bcac82a65ab62025-02-03T06:05:27ZengWileyJournal of Diabetes Research2314-67452314-67532021-01-01202110.1155/2021/66148486614848ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial CellsJian-kun Deng0Xueqin Zhang1Hong-luan Wu2Yu Gan3Ling Ye4Huijuan Zheng5Zebing Zhu6Wei Jing Liu7Hua-feng Liu8Institute of Nephrology, Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, Zhanjiang, Guangdong 524001, ChinaRenal Research Institution of Beijing University of Chinese Medicine, and Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, ChinaInstitute of Nephrology, Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, Zhanjiang, Guangdong 524001, ChinaInstitute of Nephrology, Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, Zhanjiang, Guangdong 524001, ChinaInstitute of Nephrology, Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, Zhanjiang, Guangdong 524001, ChinaRenal Research Institution of Beijing University of Chinese Medicine, and Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, ChinaRenal Research Institution of Beijing University of Chinese Medicine, and Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, ChinaInstitute of Nephrology, Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, Zhanjiang, Guangdong 524001, ChinaInstitute of Nephrology, Zhanjiang Key Laboratory of Prevention and Management of Chronic Kidney Disease, Guangdong Medical University, Zhanjiang, Guangdong 524001, ChinaERK, an extracellular signal-regulated protein kinase, is involved in various biological responses, such as cell proliferation and differentiation, cell morphology maintenance, cytoskeletal construction, apoptosis, and canceration of cells. In this study, we focused on ERK pathway on cellular injury and autophagy-associated adaptive response in urinary protein-irritated renal tubular epithelial cells and explored the potential mechanisms underlying it. By using antioxidants N-acetylcysteine and catalase, we found that ERK pathway was activated by a reactive oxygen species- (ROS-) dependent mechanism after exposure to urinary proteins. What is more, ERK inhibitor U0126 could decrease the release of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and the number of apoptotic cells induced by urinary proteins, indicating the damaging effects of ERK pathway in mediating cellular injury and apoptosis in HK-2 cells. Interestingly, we also found that the increased expression of microtubule-associated protein 1 light chain 3 (LC3)-II (a key marker of autophagy) and the decreased expression of p62 (autophagic substrate) induced by urinary proteins were reversed by U0126, suggesting autophagy was activated by ERK pathway. Furthermore, rapamycin reduced urinary protein-induced NGAL and KIM-1 secretion and cell growth inhibition, while chloroquine played the opposite effect, indicating that autophagy activation by ERK pathway was an adaptive response in the exposure to urinary proteins. Taken together, our results indicate that activated ROS-ERK pathway can induce cellular injury and in the meantime provide an autophagy-associated adaptive response in urinary protein-irritated renal tubular epithelial cells.http://dx.doi.org/10.1155/2021/6614848 |
| spellingShingle | Jian-kun Deng Xueqin Zhang Hong-luan Wu Yu Gan Ling Ye Huijuan Zheng Zebing Zhu Wei Jing Liu Hua-feng Liu ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells Journal of Diabetes Research |
| title | ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells |
| title_full | ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells |
| title_fullStr | ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells |
| title_full_unstemmed | ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells |
| title_short | ROS-ERK Pathway as Dual Mediators of Cellular Injury and Autophagy-Associated Adaptive Response in Urinary Protein-Irritated Renal Tubular Epithelial Cells |
| title_sort | ros erk pathway as dual mediators of cellular injury and autophagy associated adaptive response in urinary protein irritated renal tubular epithelial cells |
| url | http://dx.doi.org/10.1155/2021/6614848 |
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