Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury.
The podocyte functions as a glomerular filtration barrier. Autophagy of postmitotic cells is an important protective mechanism that is essential for maintaining the homeostasis of podocytes. Exploring an in vivo rat model of passive Heymann nephritis and an in vitro model of puromycin amino nucleoti...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3648526?pdf=render |
| _version_ | 1818363100612526080 |
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| author | Lingling Wu Zhe Feng Shaoyuan Cui Kai Hou Li Tang Jianhui Zhou Guangyan Cai Yuansheng Xie Quan Hong Bo Fu Xiangmei Chen |
| author_facet | Lingling Wu Zhe Feng Shaoyuan Cui Kai Hou Li Tang Jianhui Zhou Guangyan Cai Yuansheng Xie Quan Hong Bo Fu Xiangmei Chen |
| author_sort | Lingling Wu |
| collection | DOAJ |
| description | The podocyte functions as a glomerular filtration barrier. Autophagy of postmitotic cells is an important protective mechanism that is essential for maintaining the homeostasis of podocytes. Exploring an in vivo rat model of passive Heymann nephritis and an in vitro model of puromycin amino nucleotide (PAN)-cultured podocytes, we examined the specific mechanisms underlying changing autophagy levels and podocyte injury. In the passive Heymann nephritis model rats, the mammalian target-of-rapamycin (mTOR) levels were upregulated in injured podocytes while autophagy was inhibited. In PAN-treated podocytes, mTOR lowered the level of autophagy through the mTOR-ULK1 pathway resulting in damaged podocytes. Rapamycin treatment of these cells reduced podocyte injury by raising the levels of autophagy. These in vivo and in vitro experiments demonstrate that podocyte injury is associated with changes in autophagy levels, and that rapamycin can reduce podocyte injury by increasing autophagy levels via inhibition of the mTOR-ULK1 pathway. These results provide an important theoretical basis for future treatment of diseases involving podocyte injury. |
| first_indexed | 2024-12-13T21:43:06Z |
| format | Article |
| id | doaj.art-63b1826906ad4139aed5357d09742d49 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:43:06Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-63b1826906ad4139aed5357d09742d492022-12-21T23:30:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0185e6379910.1371/journal.pone.0063799Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury.Lingling WuZhe FengShaoyuan CuiKai HouLi TangJianhui ZhouGuangyan CaiYuansheng XieQuan HongBo FuXiangmei ChenThe podocyte functions as a glomerular filtration barrier. Autophagy of postmitotic cells is an important protective mechanism that is essential for maintaining the homeostasis of podocytes. Exploring an in vivo rat model of passive Heymann nephritis and an in vitro model of puromycin amino nucleotide (PAN)-cultured podocytes, we examined the specific mechanisms underlying changing autophagy levels and podocyte injury. In the passive Heymann nephritis model rats, the mammalian target-of-rapamycin (mTOR) levels were upregulated in injured podocytes while autophagy was inhibited. In PAN-treated podocytes, mTOR lowered the level of autophagy through the mTOR-ULK1 pathway resulting in damaged podocytes. Rapamycin treatment of these cells reduced podocyte injury by raising the levels of autophagy. These in vivo and in vitro experiments demonstrate that podocyte injury is associated with changes in autophagy levels, and that rapamycin can reduce podocyte injury by increasing autophagy levels via inhibition of the mTOR-ULK1 pathway. These results provide an important theoretical basis for future treatment of diseases involving podocyte injury.http://europepmc.org/articles/PMC3648526?pdf=render |
| spellingShingle | Lingling Wu Zhe Feng Shaoyuan Cui Kai Hou Li Tang Jianhui Zhou Guangyan Cai Yuansheng Xie Quan Hong Bo Fu Xiangmei Chen Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury. PLoS ONE |
| title | Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury. |
| title_full | Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury. |
| title_fullStr | Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury. |
| title_full_unstemmed | Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury. |
| title_short | Rapamycin upregulates autophagy by inhibiting the mTOR-ULK1 pathway, resulting in reduced podocyte injury. |
| title_sort | rapamycin upregulates autophagy by inhibiting the mtor ulk1 pathway resulting in reduced podocyte injury |
| url | http://europepmc.org/articles/PMC3648526?pdf=render |
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