LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis
Abstract Background Long non-coding RNAs (lncRNAs) are widely reported to be involved in the development of human diseases. HLA complex P5 (HCP5) deregulation is associated with various diseases. However, the function of HCP5 in diabetic nephropathy (DN) is unclear. Methods Human glomerular mesangia...
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| Format: | Article |
| Language: | English |
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BMC
2021-06-01
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| Series: | BMC Endocrine Disorders |
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| Online Access: | https://doi.org/10.1186/s12902-021-00781-y |
| _version_ | 1818456510531895296 |
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| author | Xuan Wang Yan Liu Jian Rong Kai Wang |
| author_facet | Xuan Wang Yan Liu Jian Rong Kai Wang |
| author_sort | Xuan Wang |
| collection | DOAJ |
| description | Abstract Background Long non-coding RNAs (lncRNAs) are widely reported to be involved in the development of human diseases. HLA complex P5 (HCP5) deregulation is associated with various diseases. However, the function of HCP5 in diabetic nephropathy (DN) is unclear. Methods Human glomerular mesangial cells (HGMCs) were treated with high glucose (HG) to establish DN cell models. The expression of HCP5, miR-93-5p and high mobility group AT-hook 2 (HMGA2) mRNA was detected using quantitative polymerase chain reaction (QPCR). Cell proliferation and cell apoptosis were assessed using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of apoptosis- and fibrosis-related proteins and HMGA2 protein was quantified by western blot. The release of pro-inflammatory factor was checked using enzyme-linked immunosorbent assay (ELISA). The predicted relationship between miR-93-5p and HCP5 or HMGA2 was verified using dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay. Results The expression of HCP5 and HMGA2 was enhanced, while the expression of miR-93-5p was declined in DN serum samples and HG-treated HGMCs. HCP5 knockdown or miR-93-5p restoration ameliorated HG-induced HGMC proliferation, fibrosis and inflammation. MiR-93-5p was a target of HCP5, and miR-93-5p inhibition reversed the effects caused by HCP5 knockdown. Moreover, HMGA2 was a target of miR-93-5p, and HMGA2 overexpression abolished the effects of miR-93-5p restoration. HCP5 knockdown inhibited the AKT/mTOR signaling pathway. Conclusion HCP5 was implicated in DN progression by modulating the miR-93-5p/HMGA2 axis, which provided new insights into the understanding of DN pathogenesis. |
| first_indexed | 2024-12-14T22:27:49Z |
| format | Article |
| id | doaj.art-284ca26edc3140de9904ca48f64ac2f7 |
| institution | Directory Open Access Journal |
| issn | 1472-6823 |
| language | English |
| last_indexed | 2024-12-14T22:27:49Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Endocrine Disorders |
| spelling | doaj.art-284ca26edc3140de9904ca48f64ac2f72022-12-21T22:45:18ZengBMCBMC Endocrine Disorders1472-68232021-06-0121111410.1186/s12902-021-00781-yLncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axisXuan Wang0Yan Liu1Jian Rong2Kai Wang3Department of International Medical Center, Tianjin HospitalDepartment of Spine Surgery, Tianjin Union Medical CenterDepartment of Emergency internal medicine, Tianjin HospitalDepartment of International Medical Center, Tianjin HospitalAbstract Background Long non-coding RNAs (lncRNAs) are widely reported to be involved in the development of human diseases. HLA complex P5 (HCP5) deregulation is associated with various diseases. However, the function of HCP5 in diabetic nephropathy (DN) is unclear. Methods Human glomerular mesangial cells (HGMCs) were treated with high glucose (HG) to establish DN cell models. The expression of HCP5, miR-93-5p and high mobility group AT-hook 2 (HMGA2) mRNA was detected using quantitative polymerase chain reaction (QPCR). Cell proliferation and cell apoptosis were assessed using cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The expression of apoptosis- and fibrosis-related proteins and HMGA2 protein was quantified by western blot. The release of pro-inflammatory factor was checked using enzyme-linked immunosorbent assay (ELISA). The predicted relationship between miR-93-5p and HCP5 or HMGA2 was verified using dual-luciferase reporter assay, pull-down assay or RNA immunoprecipitation (RIP) assay. Results The expression of HCP5 and HMGA2 was enhanced, while the expression of miR-93-5p was declined in DN serum samples and HG-treated HGMCs. HCP5 knockdown or miR-93-5p restoration ameliorated HG-induced HGMC proliferation, fibrosis and inflammation. MiR-93-5p was a target of HCP5, and miR-93-5p inhibition reversed the effects caused by HCP5 knockdown. Moreover, HMGA2 was a target of miR-93-5p, and HMGA2 overexpression abolished the effects of miR-93-5p restoration. HCP5 knockdown inhibited the AKT/mTOR signaling pathway. Conclusion HCP5 was implicated in DN progression by modulating the miR-93-5p/HMGA2 axis, which provided new insights into the understanding of DN pathogenesis.https://doi.org/10.1186/s12902-021-00781-yHCP5miR-93-5pHMGA2Diabetic nephropathyHigh glucose |
| spellingShingle | Xuan Wang Yan Liu Jian Rong Kai Wang LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis BMC Endocrine Disorders HCP5 miR-93-5p HMGA2 Diabetic nephropathy High glucose |
| title | LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis |
| title_full | LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis |
| title_fullStr | LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis |
| title_full_unstemmed | LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis |
| title_short | LncRNA HCP5 knockdown inhibits high glucose-induced excessive proliferation, fibrosis and inflammation of human glomerular mesangial cells by regulating the miR-93-5p/HMGA2 axis |
| title_sort | lncrna hcp5 knockdown inhibits high glucose induced excessive proliferation fibrosis and inflammation of human glomerular mesangial cells by regulating the mir 93 5p hmga2 axis |
| topic | HCP5 miR-93-5p HMGA2 Diabetic nephropathy High glucose |
| url | https://doi.org/10.1186/s12902-021-00781-y |
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