Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway
Abstract Background Diabetic nephropathy (DN) is the leading cause of the end-stage renal disease (ESRD). The proliferation and apoptosis of mesangial cells induced by the activated Wnt/β-catenin pathway is crucial in DN. Trigonelline (TRL) is an alkaloid that has been shown to decrease proteinuria...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Diabetology & Metabolic Syndrome |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13098-022-00798-w |
| _version_ | 1818284293203427328 |
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| author | Chen Chen Yan Shi Jiulong Ma Zhen Chen Ming Zhang Yan Zhao |
| author_facet | Chen Chen Yan Shi Jiulong Ma Zhen Chen Ming Zhang Yan Zhao |
| author_sort | Chen Chen |
| collection | DOAJ |
| description | Abstract Background Diabetic nephropathy (DN) is the leading cause of the end-stage renal disease (ESRD). The proliferation and apoptosis of mesangial cells induced by the activated Wnt/β-catenin pathway is crucial in DN. Trigonelline (TRL) is an alkaloid that has been shown to decrease proteinuria and protect the renal function in DN. However, the effect of TRL on the Wnt/β-catenin pathway of mesangial cells is unclear. Methods As a cellular DN model, human mesangial cells (HMCs) were treated with high-glucose (HG). β-Catenin plasmid and control knockdown plasmids were transfected into HG-treated HMCs as β-catenin pcDNA and β-catenin siRNA groups, respectively. Cell viability was measured by MTT assay. Flow cytometry was used to detect the cell cycle. Cell apoptosis was evaluated by flow cytometry and terminal dUTP transferase nick end labeling (TUNEL) assay. mRNA expression of Wnt1, Wnt3a, Wnt4, Wnt5a, β-catenin, TCF4, Cyclin D1, and CDK4 were detected by qRT-PCR. Protein expression of Wnt4, Wnt5a, nucleus-β-catenin, TCF4, Cyclin D1, and CDK4 were detected by western blotting. Results TRL significantly inhibited HG-induced HMCs viability over three-time points measured (24, 48, and 72 h). In addition, TRL suppressed the levels of fibronectin (FN) and collagen IV (Col IV) in HG-stimulated HMCs. Furthermore, TRL efficiently inhibited the activation of the Wnt/β-catenin signaling pathway in HG-stimulated HMCs. Taken together, these data indicated that TRL inhibited HG-induced HMCs proliferation and ECM expression via the modulation of the Wnt signaling pathway. Conclusions TRL reduces HG-induced cell injury by regulating the Wnt/β-catenin signaling pathway. |
| first_indexed | 2024-12-13T00:50:30Z |
| format | Article |
| id | doaj.art-769b13a253474083b4992521aa8e3256 |
| institution | Directory Open Access Journal |
| issn | 1758-5996 |
| language | English |
| last_indexed | 2024-12-13T00:50:30Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj.art-769b13a253474083b4992521aa8e32562022-12-22T00:04:57ZengBMCDiabetology & Metabolic Syndrome1758-59962022-02-0114111310.1186/s13098-022-00798-wTrigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathwayChen Chen0Yan Shi1Jiulong Ma2Zhen Chen3Ming Zhang4Yan Zhao5College of Pharmacy, Jilin UniversityCollege of Pharmacy, Jilin UniversityCollege of Pharmacy, Jilin UniversityCollege of Pharmacy, Jilin UniversityCollege of Pharmacy, Jilin UniversityPhysical Examination Center, Jilin University Second HospitalAbstract Background Diabetic nephropathy (DN) is the leading cause of the end-stage renal disease (ESRD). The proliferation and apoptosis of mesangial cells induced by the activated Wnt/β-catenin pathway is crucial in DN. Trigonelline (TRL) is an alkaloid that has been shown to decrease proteinuria and protect the renal function in DN. However, the effect of TRL on the Wnt/β-catenin pathway of mesangial cells is unclear. Methods As a cellular DN model, human mesangial cells (HMCs) were treated with high-glucose (HG). β-Catenin plasmid and control knockdown plasmids were transfected into HG-treated HMCs as β-catenin pcDNA and β-catenin siRNA groups, respectively. Cell viability was measured by MTT assay. Flow cytometry was used to detect the cell cycle. Cell apoptosis was evaluated by flow cytometry and terminal dUTP transferase nick end labeling (TUNEL) assay. mRNA expression of Wnt1, Wnt3a, Wnt4, Wnt5a, β-catenin, TCF4, Cyclin D1, and CDK4 were detected by qRT-PCR. Protein expression of Wnt4, Wnt5a, nucleus-β-catenin, TCF4, Cyclin D1, and CDK4 were detected by western blotting. Results TRL significantly inhibited HG-induced HMCs viability over three-time points measured (24, 48, and 72 h). In addition, TRL suppressed the levels of fibronectin (FN) and collagen IV (Col IV) in HG-stimulated HMCs. Furthermore, TRL efficiently inhibited the activation of the Wnt/β-catenin signaling pathway in HG-stimulated HMCs. Taken together, these data indicated that TRL inhibited HG-induced HMCs proliferation and ECM expression via the modulation of the Wnt signaling pathway. Conclusions TRL reduces HG-induced cell injury by regulating the Wnt/β-catenin signaling pathway.https://doi.org/10.1186/s13098-022-00798-wDiabetic nephropathyTrigonellineMesangial cellsWnt/β-cateninApoptosis |
| spellingShingle | Chen Chen Yan Shi Jiulong Ma Zhen Chen Ming Zhang Yan Zhao Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway Diabetology & Metabolic Syndrome Diabetic nephropathy Trigonelline Mesangial cells Wnt/β-catenin Apoptosis |
| title | Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway |
| title_full | Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway |
| title_fullStr | Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway |
| title_full_unstemmed | Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway |
| title_short | Trigonelline reverses high glucose-induced proliferation, fibrosis of mesangial cells via modulation of Wnt signaling pathway |
| title_sort | trigonelline reverses high glucose induced proliferation fibrosis of mesangial cells via modulation of wnt signaling pathway |
| topic | Diabetic nephropathy Trigonelline Mesangial cells Wnt/β-catenin Apoptosis |
| url | https://doi.org/10.1186/s13098-022-00798-w |
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