Peptide corresponding to the C terminus of tissue factor pathway inhibitor inhibits mesangial cell proliferation and activation in vivo.
Mesangial cells (MsCs) are one of the resident cell types in the glomerulus and are important with respect to its function and structure. The activation and proliferation of MsCs occur in several types of glomerulonephritis, particularly proliferative glomerulonephritis, producing a series of protein factors and matrix components that impair the normal structure and function of the glomerulus. To inhibit proliferation or induction of apoptosis is considered to be one mechanism that can be used to treat these diseases. In previous studies, we found that the tissue factor pathway inhibitor (TFPI) induces the apoptosis of cultured rat MsCs. Here, we expressed a series of TFPI fragments as fusion proteins to maltose binding protein (MBP-TFPI(162-188), MBP-TFPI(187-241), MBP-TFPI(240-276), MBP-TFPI(162-241), MBP-TFPI(187-276) and MBP-TFPI(162-276)) and applied them to cultured rat mesangial cells. The C terminus of TFPI, a peptide corresponding to residues 240-276 of TFPI, was confirmed to induce apoptosis of MsCs in vitro. To observe the effect of this peptide on MsCs in vivo, we performed intramuscular gene transfer treatment on a rat model of proliferative glomerulonephritis with a plasmid containing the gene for the C terminus of TFPI. This revealed that the C terminus of TFPI exhibited suppressive effects on the activation and proliferation of MsCs and, thereby, improved renal function. Our data indicate that the C terminus of TFPI could be used in the treatment of proliferative glomerulonephritis.
Liang
Wang
W
Key Laboratory of Molecular Medicine, Ministry of Education, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Cheng
Juan
J
Liu
Rui
R
Wang
Ji-ping
JP
Mu
Jin-gui
JG
Wang
Qing-hua
QH
Wang
Hui-jun
HJ
Ma
Duan
D
D000595:Amino Acid Sequence; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D050527:Mesangial Cells / Q000166:cytology* / Q000187:drug effects*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017386:Sequence Homology, Amino Acid
D008074:Lipoproteins; D010455:Peptides; C051928:lipoprotein-associated coagulation inhibitor