RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency
Abstract To determine whether p16INK4a deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1−/−) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16INK4a double-knockout, and Bmi-1−/− and wild-t...
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| Language: | English |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06868-8 |
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| author | Jianliang Jin Jianguo Tao Xin Gu Zhenzhen Yu Rong Wang Guoping Zuo Qing Li Xianhui Lv Dengshun Miao |
| author_facet | Jianliang Jin Jianguo Tao Xin Gu Zhenzhen Yu Rong Wang Guoping Zuo Qing Li Xianhui Lv Dengshun Miao |
| author_sort | Jianliang Jin |
| collection | DOAJ |
| description | Abstract To determine whether p16INK4a deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1−/−) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16INK4a double-knockout, and Bmi-1−/− and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1. Our results demonstrated that p16INK4a deletion largely rescued renal aging phenotypes caused by Bmi-1 deficiency, including impaired renal structure and function, decreased proliferation, increased apoptosis, senescence and SASP, DNA damage, NF-κB and TGF-β1/Smad signal activation, inflammatory cell infiltration, and tubulointerstitial fibrosis and tubular atrophy. P16INK4a deletion also promoted proliferation, reduced senescence and SASP of RIFs and subsequently inhibited EMT of Bmi-1-knockdown HK2 cells. TGF-β1 further induced the EMT of Bmi-1-knockdown HK2 cells. Thus, p16INK4a positive senescent cells would be a therapeutic target for preventing renal tubulointerstitial injury. |
| format | Article |
| id | doaj-art-4c64dd3346f74c08ba57765ffa2e2944 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-4c64dd3346f74c08ba57765ffa2e29442025-01-19T12:25:06ZengNature PortfolioScientific Reports2045-23222017-08-017111610.1038/s41598-017-06868-8RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 DeficiencyJianliang Jin0Jianguo Tao1Xin Gu2Zhenzhen Yu3Rong Wang4Guoping Zuo5Qing Li6Xianhui Lv7Dengshun Miao8The State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical UniversityThe State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical UniversityThe State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical UniversityThe State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical UniversityThe State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical UniversityLaboratory Centre for Basic Medical Sciences, Nanjing Medical UniversityDepartment of Science and Technology, Jiangsu Jiankang Vocational CollegeThe State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical UniversityThe State Key Laboratory of Reproductive Medicine; Key Laboratory for Aging & Disease, Research Centre for Bone and Stem Cells, Department of Human Anatomy, Nanjing Medical UniversityAbstract To determine whether p16INK4a deletion ameliorated renal tubulointerstitial injury by inhibiting a senescence-associated secretory phenotype (SASP) in Bmi-1-deficient (Bmi-1−/−) mice, renal phenotypes were compared among 5-week-old Bmi-1 and p16INK4a double-knockout, and Bmi-1−/− and wild-type mice. Fifth-passage renal interstitial fibroblasts (RIFs) from the three groups were analyzed for senescence and proliferation. The effect of Bmi-1 deficiency on epithelial-to-mesenchymal transition (EMT) was examined in Bmi-1-knockdown human renal proximal tubular epithelial (HK2) cells, which were treated with concentrated conditioned medium (CM) from the fifth-passage renal interstitial fibroblasts (RIFs) of above three group mice or with exogenous TGF-β1. Our results demonstrated that p16INK4a deletion largely rescued renal aging phenotypes caused by Bmi-1 deficiency, including impaired renal structure and function, decreased proliferation, increased apoptosis, senescence and SASP, DNA damage, NF-κB and TGF-β1/Smad signal activation, inflammatory cell infiltration, and tubulointerstitial fibrosis and tubular atrophy. P16INK4a deletion also promoted proliferation, reduced senescence and SASP of RIFs and subsequently inhibited EMT of Bmi-1-knockdown HK2 cells. TGF-β1 further induced the EMT of Bmi-1-knockdown HK2 cells. Thus, p16INK4a positive senescent cells would be a therapeutic target for preventing renal tubulointerstitial injury.https://doi.org/10.1038/s41598-017-06868-8 |
| spellingShingle | Jianliang Jin Jianguo Tao Xin Gu Zhenzhen Yu Rong Wang Guoping Zuo Qing Li Xianhui Lv Dengshun Miao RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency Scientific Reports |
| title | RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency |
| title_full | RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency |
| title_fullStr | RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency |
| title_full_unstemmed | RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency |
| title_short | RETRACTED ARTICLE: P16INK4a Deletion Ameliorated Renal Tubulointerstitial Injury in a Stress-induced Premature Senescence Model of Bmi-1 Deficiency |
| title_sort | retracted article p16ink4a deletion ameliorated renal tubulointerstitial injury in a stress induced premature senescence model of bmi 1 deficiency |
| url | https://doi.org/10.1038/s41598-017-06868-8 |
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