Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells
Abstract Background Poor decidualization and abnormal autophagy conditions in the endometria of adenomyosis patients have been reported previously. However, the specific regulatory mechanism of decidualization in adenomyosis and its relationship with autophagy levels have not been clarified. Methods...
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | BMC Molecular and Cell Biology |
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| Online Access: | https://doi.org/10.1186/s12860-022-00425-6 |
| _version_ | 1828309329237770240 |
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| author | Jie Mei Xiaoqiang Sheng Yuan Yan Xinyu Cai Chunxue Zhang Jiao Tian Mei Zhang Jidong Zhou Huizhi Shan Chenyang Huang |
| author_facet | Jie Mei Xiaoqiang Sheng Yuan Yan Xinyu Cai Chunxue Zhang Jiao Tian Mei Zhang Jidong Zhou Huizhi Shan Chenyang Huang |
| author_sort | Jie Mei |
| collection | DOAJ |
| description | Abstract Background Poor decidualization and abnormal autophagy conditions in the endometria of adenomyosis patients have been reported previously. However, the specific regulatory mechanism of decidualization in adenomyosis and its relationship with autophagy levels have not been clarified. Methods Endometrial tissues from adenomyosis patients and uteri from an adenomyosis mouse model were collected for the detection of different expression patterns of KLF4 and autophagy markers (LC3-B/LC3-A and Beclin-1) compared with control groups. Human endometrial stromal cells (hESCs) isolated from adenomyosis and control endometrial tissues were employed to elucidate the biological functions of KLF4 in autophagy and decidualization. Gene expression regulation was examined by quantitative real-time PCR (qRT-PCR), western blotting and luciferase reporter assays. In addition, DNA promoter-protein interactions were examined by chromatin immunoprecipitation (ChIP)/PCR assay and avidin–biotin conjugate DNA precipitation (ABCD) assay. Results KLF4 expression was decreased in endometrial tissues from adenomyosis patients compared with those from fertile controls, especially in stromal compartments. The opposite results were observed for autophagy marker (LC3-B/LC3-A and Beclin-1) expression. At the same time, KLF4 reversed the poor decidualization of hESCs from adenomyosis patients. In addition, KLF4 could induce hESC decidualization by promoting the autophagy level. Mechanistically, KLF4 bound to a conserved site in the autophagy-related 5 (ATG5) promoter region and promoted ATG5 expression. Similar expression patterns of KLF4 and autophagy markers were detected in adenomyotic mice. Conclusions KLF4 overexpression increases the autophagy level of hESCs by transcriptionally promoting ATG5 expression, and abnormally decreased KLF4 in adenomyosis impairs hESC decidualization by repressing autophagy. |
| first_indexed | 2024-04-13T15:27:56Z |
| format | Article |
| id | doaj.art-8acfc17a141a4fc398f7c2d696d3733f |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-04-13T15:27:56Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-8acfc17a141a4fc398f7c2d696d3733f2022-12-22T02:41:28ZengBMCBMC Molecular and Cell Biology2661-88502022-06-0123111210.1186/s12860-022-00425-6Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cellsJie Mei0Xiaoqiang Sheng1Yuan Yan2Xinyu Cai3Chunxue Zhang4Jiao Tian5Mei Zhang6Jidong Zhou7Huizhi Shan8Chenyang Huang9Center for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolDepartment of Obstetrics and Gynecology, Nanjing First Hospital, Nanjing Medical UniversityCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolCenter for Reproductive Medicine and Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical SchoolAbstract Background Poor decidualization and abnormal autophagy conditions in the endometria of adenomyosis patients have been reported previously. However, the specific regulatory mechanism of decidualization in adenomyosis and its relationship with autophagy levels have not been clarified. Methods Endometrial tissues from adenomyosis patients and uteri from an adenomyosis mouse model were collected for the detection of different expression patterns of KLF4 and autophagy markers (LC3-B/LC3-A and Beclin-1) compared with control groups. Human endometrial stromal cells (hESCs) isolated from adenomyosis and control endometrial tissues were employed to elucidate the biological functions of KLF4 in autophagy and decidualization. Gene expression regulation was examined by quantitative real-time PCR (qRT-PCR), western blotting and luciferase reporter assays. In addition, DNA promoter-protein interactions were examined by chromatin immunoprecipitation (ChIP)/PCR assay and avidin–biotin conjugate DNA precipitation (ABCD) assay. Results KLF4 expression was decreased in endometrial tissues from adenomyosis patients compared with those from fertile controls, especially in stromal compartments. The opposite results were observed for autophagy marker (LC3-B/LC3-A and Beclin-1) expression. At the same time, KLF4 reversed the poor decidualization of hESCs from adenomyosis patients. In addition, KLF4 could induce hESC decidualization by promoting the autophagy level. Mechanistically, KLF4 bound to a conserved site in the autophagy-related 5 (ATG5) promoter region and promoted ATG5 expression. Similar expression patterns of KLF4 and autophagy markers were detected in adenomyotic mice. Conclusions KLF4 overexpression increases the autophagy level of hESCs by transcriptionally promoting ATG5 expression, and abnormally decreased KLF4 in adenomyosis impairs hESC decidualization by repressing autophagy.https://doi.org/10.1186/s12860-022-00425-6Krüppel-like factor 4AdenomyosisImpaired decidualizationAutophagyTranscriptional regulationAutophagy-related 5 |
| spellingShingle | Jie Mei Xiaoqiang Sheng Yuan Yan Xinyu Cai Chunxue Zhang Jiao Tian Mei Zhang Jidong Zhou Huizhi Shan Chenyang Huang Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells BMC Molecular and Cell Biology Krüppel-like factor 4 Adenomyosis Impaired decidualization Autophagy Transcriptional regulation Autophagy-related 5 |
| title | Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells |
| title_full | Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells |
| title_fullStr | Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells |
| title_full_unstemmed | Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells |
| title_short | Decreased Krüppel-like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells |
| title_sort | decreased kruppel like factor 4 in adenomyosis impairs decidualization by repressing autophagy in human endometrial stromal cells |
| topic | Krüppel-like factor 4 Adenomyosis Impaired decidualization Autophagy Transcriptional regulation Autophagy-related 5 |
| url | https://doi.org/10.1186/s12860-022-00425-6 |
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