Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis
Abstract To explore the role of suppressor of cytokine signaling‐3 (SOCS‐3) in mesangial proliferative glomerulonephritis (MsPGN). SOCS‐3 expression in kidney tissues from MsPGN patients was detected using immunohistochemistry. Double immunofluorescence staining was performed to investigate the loca...
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| Format: | Article |
| Language: | English |
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Wiley
2021-10-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.12415 |
| _version_ | 1818691892167049216 |
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| author | Min Liu Ya‐Chao Wang Jun Zhou |
| author_facet | Min Liu Ya‐Chao Wang Jun Zhou |
| author_sort | Min Liu |
| collection | DOAJ |
| description | Abstract To explore the role of suppressor of cytokine signaling‐3 (SOCS‐3) in mesangial proliferative glomerulonephritis (MsPGN). SOCS‐3 expression in kidney tissues from MsPGN patients was detected using immunohistochemistry. Double immunofluorescence staining was performed to investigate the localization of SOCS‐3 with α‐SMA in glomeruli. Heminephrectomized wild‐type (WT) and SOCS‐3−/− (KO) mice were injected with Habu‐snake venom (HSV) to establish MsPGN models, and renal function were compared. Simultaneously, immunofluorescence, periodic acid‐Schiff staining, Picrosirius red staining, as well as immunohistochemistry for PCNA, MAC‐2 and type IV collagen in glomeruli were performed. In addition, primary mouse renal mesangial cells and SV40 MES‐13 cells were transfected with SOCS‐3 siRNA or SOCS‐3 lentiviral activation particles, followed by EdU assay, flow cytometry, quantitative reverse transcription‐polymerase chain reaction, and Western blotting. Mesangial SOCS‐3 expression was enhanced in glomeruli of MsPGN patients, and SOCS‐3 was well co‐localized with activated α‐SMA. After HSV injection, WT and KO mice presented with the increases in the serum creatinine, urea nitrogen, and urinary protein, especially in KO mice. Besides, SOCS‐3−/− alleviated the hyperplasia of glomerular MCs in MsPGN mice, with the reductions in PCNA, MAC‐2, and collagen deposition. Furthermore, SOCS‐3 inhibition reduced the cell proportion at S phase to suppress cell proliferation, with the downregulations of Cyclin A, Cyclin D1, PCNA, and Ki‐67. SOCS‐3 knockout can alleviate the hyperplasia of glomerular MCs in MsPGN mice via affecting the cell cycle and proliferation of MCs, thus being a potential therapeutic target for MsPGN. |
| first_indexed | 2024-12-17T12:49:06Z |
| format | Article |
| id | doaj.art-7762808082dd43c3abd51f6912d87bbf |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-12-17T12:49:06Z |
| publishDate | 2021-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-7762808082dd43c3abd51f6912d87bbf2022-12-21T21:47:39ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502021-10-01371087288210.1002/kjm2.12415Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritisMin Liu0Ya‐Chao Wang1Jun Zhou2Department of Nephrology Wuhan Asia General Hospital Wuhan ChinaDepartment of Nephrology Wuhan Asia General Hospital Wuhan ChinaDepartment of Paediatrics Xiaogan Central Hospital Affiliated with Wuhan University of Science and Technology Xiaogan Hubei ChinaAbstract To explore the role of suppressor of cytokine signaling‐3 (SOCS‐3) in mesangial proliferative glomerulonephritis (MsPGN). SOCS‐3 expression in kidney tissues from MsPGN patients was detected using immunohistochemistry. Double immunofluorescence staining was performed to investigate the localization of SOCS‐3 with α‐SMA in glomeruli. Heminephrectomized wild‐type (WT) and SOCS‐3−/− (KO) mice were injected with Habu‐snake venom (HSV) to establish MsPGN models, and renal function were compared. Simultaneously, immunofluorescence, periodic acid‐Schiff staining, Picrosirius red staining, as well as immunohistochemistry for PCNA, MAC‐2 and type IV collagen in glomeruli were performed. In addition, primary mouse renal mesangial cells and SV40 MES‐13 cells were transfected with SOCS‐3 siRNA or SOCS‐3 lentiviral activation particles, followed by EdU assay, flow cytometry, quantitative reverse transcription‐polymerase chain reaction, and Western blotting. Mesangial SOCS‐3 expression was enhanced in glomeruli of MsPGN patients, and SOCS‐3 was well co‐localized with activated α‐SMA. After HSV injection, WT and KO mice presented with the increases in the serum creatinine, urea nitrogen, and urinary protein, especially in KO mice. Besides, SOCS‐3−/− alleviated the hyperplasia of glomerular MCs in MsPGN mice, with the reductions in PCNA, MAC‐2, and collagen deposition. Furthermore, SOCS‐3 inhibition reduced the cell proportion at S phase to suppress cell proliferation, with the downregulations of Cyclin A, Cyclin D1, PCNA, and Ki‐67. SOCS‐3 knockout can alleviate the hyperplasia of glomerular MCs in MsPGN mice via affecting the cell cycle and proliferation of MCs, thus being a potential therapeutic target for MsPGN.https://doi.org/10.1002/kjm2.12415cell cycleMsPGNPCNAproliferationSOCS‐3 |
| spellingShingle | Min Liu Ya‐Chao Wang Jun Zhou Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis Kaohsiung Journal of Medical Sciences cell cycle MsPGN PCNA proliferation SOCS‐3 |
| title | Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis |
| title_full | Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis |
| title_fullStr | Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis |
| title_full_unstemmed | Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis |
| title_short | Inhibition of suppressor of cytokine signaling‐3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis |
| title_sort | inhibition of suppressor of cytokine signaling 3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis |
| topic | cell cycle MsPGN PCNA proliferation SOCS‐3 |
| url | https://doi.org/10.1002/kjm2.12415 |
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