17β estradiol regulates adhesion molecule expression in mesangial cells during glomerulonephritis.
We showed previously that 17β estradiol (E2) led to improved survival in nephrotoxic serum induced nephritis (NTN) in male mice. In this study we determined whether E2 regulates vascular cell adhesion molecule (VCAM)-1, an adhesion molecule that is upregulated in kidney during autoimmune nephritis, in mesangial cells (MC). We show that E2 inhibited VCAM-1 up-regulation in kidneys in vivo during NTN, and in MCs upon TNFα stimulation. VCAM-1 up-regulation in MCs was controlled by the transcription factor NFκB. E2 inhibited RNA polymerase II recruitment to the VCAM-1 promoter, but not p65 recruitment. Interestingly E2 inhibited TNFα stimulated interaction between poly (ADP-ribose) polymerase-1 (PARP-1) and p65. As PARP-1 is required for VCAM-1 upregulation in MCs, our data suggest that E2 may inhibit pre-initiation complex formation at VCAM-1 promoter by inhibiting PARP-1 recruitment to p65. We propose that E2 plays an important role in regulating renal inflammation locally.
Rheumatology Section, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA.
Neelakshi R
NR
Jog
Rheumatology Section, Department of Medicine, Temple University School of Medicine, Philadelphia, PA, USA. Electronic address: roc@temple.edu.
Roberto
R
Caricchio
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005921:Glomerulonephritis; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D012319:RNA Polymerase II / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects* / Q000235:genetics
D004967:Estrogens; D012333:RNA, Messenger; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D019010:Vascular Cell Adhesion Molecule-1; D004958:Estradiol; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D012319:RNA Polymerase II
Estrogen; Mesangial cells; Nephritis; VCAM