Protease nexin 1 in the murine kidney: glomerular localization and up-regulation in glomerulopathies.
Protease nexin 1 (PN-1), a potent serpin-class antiprotease, is thought to be synthesized in the murine kidney. However, neither the cellular localization of PN-1 synthesis nor its role has yet been defined. To address these questions, we determined by in situ hybridizations RNase protection assay and immunoblotting, the sites of PN-1 mRNA accumulation in normal mouse kidneys and the modulation of PN-1 expression in several pathological conditions. In normal kidneys, PN-1 mRNA was detected primarily in glomeruli, most likely in mesangial cells. The glomerular expression of PN-1 was substantially enhanced not only in lupus-like glomerulonephritis (induced by IgG3 monoclonal rheumatoid factors or occurring spontaneously in lupus-prone mice), but also in mild glomerular lesions associated with intracapillary thrombi induced by IgG3 anti-trinitrophenyl monoclonal antibodies. In contrast, no modulation of PN-1 mRNA levels was observed during the course of lipopolysaccharide-induced acute tubular necrosis. A constitutive PN-1 gene expression and its up-regulation during glomerular injury suggest a possible role for PN-1 in glomerular biology. In view of its high inhibitory activity towards thrombin, mesangial PN-1 may be involved in the control of glomerular coagulation following initial glomerular injuries.
Moll
S
S
Department of Pathology, University of Geneva Medical School, Geneva, Switzerland.
Schaeren-Wiemers
N
N
Wohlwend
A
A
Pastore
Y
Y
Fulpius
T
T
Monard
D
D
Sappino
A P
AP
Schifferli
J A
JA
Vassalli
J D
JD
Izui
S
S
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism*; D008181:Lupus Nephritis / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D058255:Protease Nexins; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D015854:Up-Regulation
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D017395:Plasminogen Activator Inhibitor 1; D058255:Protease Nexins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D015842:Serine Proteinase Inhibitors