VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions
High glucose-mediated tubular injury contributes to the development and progression of diabetic nephropathy through renal tubulointerstitial fibrosis. V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein, is a complement receptor. Although the role of epithelial–mesenchymal...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Life |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2075-1729/10/12/354 |
| _version_ | 1797544325843779584 |
|---|---|
| author | Eun-Yeung Gong Hyung Ah Jo Sang Hyun Park Dae Ryong Cha Dae Young Hur Sang Youb Han |
| author_facet | Eun-Yeung Gong Hyung Ah Jo Sang Hyun Park Dae Ryong Cha Dae Young Hur Sang Youb Han |
| author_sort | Eun-Yeung Gong |
| collection | DOAJ |
| description | High glucose-mediated tubular injury contributes to the development and progression of diabetic nephropathy through renal tubulointerstitial fibrosis. V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein, is a complement receptor. Although the role of epithelial–mesenchymal transition (EMT) has been reported in several diseases, little is known about its relationship with VSIG4 under diabetic conditions. This study aimed to investigate the role of VSIG4 in human tubule cells stimulated by high glucose (HG, 55 mM). HG upregulated both mRNA and protein levels of VSIG4 in proximal tubule cells (HK-2 cells) and Madin Darby Canine Kidney cells. These upregulations were accompanied by increased expression of mesenchymal markers such as fibronectin, N-cadherin, matrix metalloproteinase 9, and vimentin, and by decreased expression of the epithelial marker, E-cadherin. The siRNA-mediated inhibition of VSIG4 in HK-2 cells restored the dysregulation of EMT in cells. Interestingly, VSIG4 inhibition did not affect the expression of transforming growth factor (TGF)-β, whereas inhibition of TGF-β reduced VSIG4 expression, subsequently suppressing fibrosis markers. These findings suggest that VSIG4 plays an important role in mediating renal tubular EMT through the downstream action of HG-induced TGF-β activation. |
| first_indexed | 2024-03-10T13:58:52Z |
| format | Article |
| id | doaj.art-2b8591792cf54a8996235a2f6d1b95e0 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T13:58:52Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-2b8591792cf54a8996235a2f6d1b95e02023-11-21T01:17:36ZengMDPI AGLife2075-17292020-12-01101235410.3390/life10120354VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose ConditionsEun-Yeung Gong0Hyung Ah Jo1Sang Hyun Park2Dae Ryong Cha3Dae Young Hur4Sang Youb Han5Department of Anatomy and Tumor Immunology, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan 47392, KoreaDepartment of Internal Medicine, Inje University College of Medicine, Ilsan-Paik Hospital, Joowha-ro 170, IlsanSeo-gu, Goyang, Gyeonggi 10380, KoreaDepartment of Urology, Inje University College of Medicine, Haeundae Paik Hospital, Haeundae-ro 875, Haeundae-gu, Busan 48108, KoreaDepartment of Internal Medicine, Korea University Ansan-Hospital, Kojan-Dong 516, Ansan, Kyungki-Do 15355, KoreaDepartment of Anatomy and Tumor Immunology, Inje University College of Medicine, 75 Bokji-ro, Busanjin-gu, Busan 47392, KoreaDepartment of Internal Medicine, Inje University College of Medicine, Ilsan-Paik Hospital, Joowha-ro 170, IlsanSeo-gu, Goyang, Gyeonggi 10380, KoreaHigh glucose-mediated tubular injury contributes to the development and progression of diabetic nephropathy through renal tubulointerstitial fibrosis. V-set immunoglobulin-domain-containing 4 (VSIG4), a B7 family-related protein, is a complement receptor. Although the role of epithelial–mesenchymal transition (EMT) has been reported in several diseases, little is known about its relationship with VSIG4 under diabetic conditions. This study aimed to investigate the role of VSIG4 in human tubule cells stimulated by high glucose (HG, 55 mM). HG upregulated both mRNA and protein levels of VSIG4 in proximal tubule cells (HK-2 cells) and Madin Darby Canine Kidney cells. These upregulations were accompanied by increased expression of mesenchymal markers such as fibronectin, N-cadherin, matrix metalloproteinase 9, and vimentin, and by decreased expression of the epithelial marker, E-cadherin. The siRNA-mediated inhibition of VSIG4 in HK-2 cells restored the dysregulation of EMT in cells. Interestingly, VSIG4 inhibition did not affect the expression of transforming growth factor (TGF)-β, whereas inhibition of TGF-β reduced VSIG4 expression, subsequently suppressing fibrosis markers. These findings suggest that VSIG4 plays an important role in mediating renal tubular EMT through the downstream action of HG-induced TGF-β activation.https://www.mdpi.com/2075-1729/10/12/354V-set immunoglobulin-domain containing 4 proteindiabetic nephropathieskidneyfibrosistransforming growth factor beta |
| spellingShingle | Eun-Yeung Gong Hyung Ah Jo Sang Hyun Park Dae Ryong Cha Dae Young Hur Sang Youb Han VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions Life V-set immunoglobulin-domain containing 4 protein diabetic nephropathies kidney fibrosis transforming growth factor beta |
| title | VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions |
| title_full | VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions |
| title_fullStr | VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions |
| title_full_unstemmed | VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions |
| title_short | VSIG4 Induces Epithelial-Mesenchymal Transition of Renal Tubular Cells under High-Glucose Conditions |
| title_sort | vsig4 induces epithelial mesenchymal transition of renal tubular cells under high glucose conditions |
| topic | V-set immunoglobulin-domain containing 4 protein diabetic nephropathies kidney fibrosis transforming growth factor beta |
| url | https://www.mdpi.com/2075-1729/10/12/354 |
| work_keys_str_mv | AT eunyeunggong vsig4inducesepithelialmesenchymaltransitionofrenaltubularcellsunderhighglucoseconditions AT hyungahjo vsig4inducesepithelialmesenchymaltransitionofrenaltubularcellsunderhighglucoseconditions AT sanghyunpark vsig4inducesepithelialmesenchymaltransitionofrenaltubularcellsunderhighglucoseconditions AT daeryongcha vsig4inducesepithelialmesenchymaltransitionofrenaltubularcellsunderhighglucoseconditions AT daeyounghur vsig4inducesepithelialmesenchymaltransitionofrenaltubularcellsunderhighglucoseconditions AT sangyoubhan vsig4inducesepithelialmesenchymaltransitionofrenaltubularcellsunderhighglucoseconditions |