title: Effects of polycystin‑1 N‑terminal fragment fusion protein on the proliferation and apoptosis of rat mesangial cells.
abstract: Mesangial proliferative glomerulonephritis (MsPGN) is characterized by widespread mesangial cell proliferation and an accumulation of extracellular matrix (ECM) in the mesangial area. In a previous study we developed a polycystin‑1 N‑terminal fragment (PC‑1 NF) fusion protein that inhibits the proliferation of cyst‑lining epithelial cells in autosomal dominant polycystic kidney disease. In addition, the PC‑1 NF fusion protein arrests the cell cycle of cancer cells at the G0/G1 phase, inhibiting their proliferation. In the present study, the effect of the PC‑1 NF fusion protein on MsPGN was investigated. It was found that the PC‑1 NF fusion protein inhibited the proliferation of rat mesangial cells and induced G0/G1 phase arrest and apoptosis in vitro. PC‑1 NF fusion protein treatment also resulted in a decrease in mRNA expression levels of proliferating cell nuclear antigen, cyclin D1 and B‑cell lymphoma‑2 (Bcl‑2) and an increase in mRNA expression levels of Bcl‑2‑associated X protein (Bax) and p21Waf1. Furthermore, a decrease in Bcl‑2, c‑fos, c‑jun and protein kinase C‑α protein levels was observed, whereas Bax protein levels increased. Additionally, PC‑1 NF fusion protein induced ECM degradation and inhibited ECM expansion. The results also demonstrated that PC‑1 NF fusion protein treatment resulted in a decrease in type IV collagen and tissue inhibitor of metalloproteinase mRNA levels but an increase in matrix metalloproteinase 2 mRNA levels. In combination, these results suggest that the PC‑1 NF fusion protein inhibits proliferation, promotes apoptosis and induces ECM degradation in MsPGN rats. This study offers novel perspectives for the treatment of MsPGN.
authors: Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors: Tianjun
authors: T
authors: Guan
authors: Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors: Qing
authors: Q
authors: Gao
authors: Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, P.R. China.
authors: Ping
authors: P
authors: Chen
authors: Division of Nephrology, Center of Kidney Disease, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors: Lili
authors: L
authors: Fu
authors: Department of Nephrology, Navy General Hospital, Beijing 100000, P.R. China.
authors: Haidan
authors: H
authors: Zhao
authors: Division of Nephrology, Center of Kidney Disease, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors: Zhuying
authors: Z
authors: Zou
authors: Division of Nephrology, Center of Kidney Disease, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
authors: Changlin
authors: C
authors: Mei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005921:Glomerulonephritis / Q000188:drug therapy; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects*; D016891:Polycystic Kidney, Autosomal Dominant / Q000188:drug therapy; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D050396:TRPP Cation Channels / Q000494:pharmacology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019938:Cyclin D1; D020778:Matrix Metalloproteinase 2; D018809:Proliferating Cell Nuclear Antigen; D051571:Protein Kinase C-alpha; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D050396:TRPP Cation Channels; D019715:Tissue Inhibitor of Metalloproteinase-1; D051028:bcl-2-Associated X Protein; C494828:Bax protein, rat; C530106:Ccnd1 protein, rat; C576839:TIMP1 protein, rat; C522363:Mmp2 protein, rat