| First Author | Liu M | Year | 2021 |
| Journal | Kaohsiung J Med Sci | Volume | 37 |
| Issue | 10 | Pages | 872-882 |
| PubMed ID | 34213074 | Mgi Jnum | J:340125 |
| Mgi Id | MGI:7506750 | Doi | 10.1002/kjm2.12415 |
| Citation | Liu M, et al. (2021) Inhibition of suppressor of cytokine signaling-3 affects mesangial cell proliferation and cell cycle in mesangioproliferative glomerulonephritis. Kaohsiung J Med Sci 37(10):872-882 |
| abstractText | 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 alpha-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 alpha-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. |
