Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the Glomerulus
In this study, we investigated the therapeutic effects and mechanisms of umbilical cord mesenchymal stem cells (UCMSCs) in diabetic nephropathy (DN) ZDF (FA/FA) rats. The therapeutic effects were assessed by renal function tests, the urinary albumin–creatinine ratio, PAS staining, electron microscop...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/jdr/6683126 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849700264397766656 |
|---|---|
| author | Shiyuan Liu Mingyao Meng Chunkai Huang Lijia He Pu Wang Zhe Tang Xi Ran Hui Gao Yangfan Guo Yan He Jian Chen Haiyan Hu Shan He Yiyi Zhao Zongliu Hou Lin Li Wenhong Li Wenju Wang Xiaodan Wang |
| author_facet | Shiyuan Liu Mingyao Meng Chunkai Huang Lijia He Pu Wang Zhe Tang Xi Ran Hui Gao Yangfan Guo Yan He Jian Chen Haiyan Hu Shan He Yiyi Zhao Zongliu Hou Lin Li Wenhong Li Wenju Wang Xiaodan Wang |
| author_sort | Shiyuan Liu |
| collection | DOAJ |
| description | In this study, we investigated the therapeutic effects and mechanisms of umbilical cord mesenchymal stem cells (UCMSCs) in diabetic nephropathy (DN) ZDF (FA/FA) rats. The therapeutic effects were assessed by renal function tests, the urinary albumin–creatinine ratio, PAS staining, electron microscopy, and TGF-β1 expression in renal tissue. Subsequently, podocyte injury in renal tissue was detected by immunofluorescence staining for podocin. To further explore the underlying mechanism, serum Angptl4 levels were measured, and Angptl4, integrin β3, fibronectin, and podocin levels in renal tissue were analysed by Western blotting. In vitro, podocytes are stimulated with high glucose and then treated with UCMSCs, and podocyte activity and the expression of synaptopodin, Angptl4, and integrin β3 were observed. UCMSC significantly improve renal function, pathological injury, and podocyte injury in the ZDF (FA/FA) rats. Western blot revealed increased expression of Angptl4, integrin β3, and fibronectin in renal tissues of the DN group, and UCMSC treatment significantly downregulated those proteins. However, UCMSC showed no effects on serum Angptl4 concentration. Podocin expression in renal tissues was significantly restored by UCMSC treatment. In vitro, podocyte activity was decreased after high glucose stimulation and improved by UCMSC treatment. UCMSC restored the expression of synaptopodin, and Angptl4 and downstream integrin β3 were also inhibited. Our study suggested that UCMSC therapy could improve renal function and renal pathological changes in ZDF (FA/FA) rats. In addition, inhibition of the Angptl4/integrin β3 pathway is the potential mechanism by which UCMSC attenuates podocyte injury in the DN model. |
| format | Article |
| id | doaj-art-7f75359d4a554da78bf77712433f4d9c |
| institution | DOAJ |
| issn | 2314-6753 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-7f75359d4a554da78bf77712433f4d9c2025-08-20T03:18:19ZengWileyJournal of Diabetes Research2314-67532025-01-01202510.1155/jdr/6683126Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the GlomerulusShiyuan Liu0Mingyao Meng1Chunkai Huang2Lijia He3Pu Wang4Zhe Tang5Xi Ran6Hui Gao7Yangfan Guo8Yan He9Jian Chen10Haiyan Hu11Shan He12Yiyi Zhao13Zongliu Hou14Lin Li15Wenhong Li16Wenju Wang17Xiaodan Wang18Yan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityYan'an Hospital Affiliated to Kunming Medical UniversityIn this study, we investigated the therapeutic effects and mechanisms of umbilical cord mesenchymal stem cells (UCMSCs) in diabetic nephropathy (DN) ZDF (FA/FA) rats. The therapeutic effects were assessed by renal function tests, the urinary albumin–creatinine ratio, PAS staining, electron microscopy, and TGF-β1 expression in renal tissue. Subsequently, podocyte injury in renal tissue was detected by immunofluorescence staining for podocin. To further explore the underlying mechanism, serum Angptl4 levels were measured, and Angptl4, integrin β3, fibronectin, and podocin levels in renal tissue were analysed by Western blotting. In vitro, podocytes are stimulated with high glucose and then treated with UCMSCs, and podocyte activity and the expression of synaptopodin, Angptl4, and integrin β3 were observed. UCMSC significantly improve renal function, pathological injury, and podocyte injury in the ZDF (FA/FA) rats. Western blot revealed increased expression of Angptl4, integrin β3, and fibronectin in renal tissues of the DN group, and UCMSC treatment significantly downregulated those proteins. However, UCMSC showed no effects on serum Angptl4 concentration. Podocin expression in renal tissues was significantly restored by UCMSC treatment. In vitro, podocyte activity was decreased after high glucose stimulation and improved by UCMSC treatment. UCMSC restored the expression of synaptopodin, and Angptl4 and downstream integrin β3 were also inhibited. Our study suggested that UCMSC therapy could improve renal function and renal pathological changes in ZDF (FA/FA) rats. In addition, inhibition of the Angptl4/integrin β3 pathway is the potential mechanism by which UCMSC attenuates podocyte injury in the DN model.http://dx.doi.org/10.1155/jdr/6683126 |
| spellingShingle | Shiyuan Liu Mingyao Meng Chunkai Huang Lijia He Pu Wang Zhe Tang Xi Ran Hui Gao Yangfan Guo Yan He Jian Chen Haiyan Hu Shan He Yiyi Zhao Zongliu Hou Lin Li Wenhong Li Wenju Wang Xiaodan Wang Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the Glomerulus Journal of Diabetes Research |
| title | Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the Glomerulus |
| title_full | Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the Glomerulus |
| title_fullStr | Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the Glomerulus |
| title_full_unstemmed | Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the Glomerulus |
| title_short | Umbilical Cord Mesenchymal Stem Cells Attenuate Podocyte Injury in Diabetic Nephropathy Rats by Inhibiting Angpltl4/Integrin β3 in the Glomerulus |
| title_sort | umbilical cord mesenchymal stem cells attenuate podocyte injury in diabetic nephropathy rats by inhibiting angpltl4 integrin β3 in the glomerulus |
| url | http://dx.doi.org/10.1155/jdr/6683126 |
| work_keys_str_mv | AT shiyuanliu umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT mingyaomeng umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT chunkaihuang umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT lijiahe umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT puwang umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT zhetang umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT xiran umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT huigao umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT yangfanguo umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT yanhe umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT jianchen umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT haiyanhu umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT shanhe umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT yiyizhao umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT zongliuhou umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT linli umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT wenhongli umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT wenjuwang umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus AT xiaodanwang umbilicalcordmesenchymalstemcellsattenuatepodocyteinjuryindiabeticnephropathyratsbyinhibitingangpltl4integrinb3intheglomerulus |