Protease nexin 1 in the murine kidney: glomerular localization and up-regulation in glomerulopathies

Kidney International
S MollS Izui

Abstract

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 ...Continue Reading

References

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Citations

Jun 3, 2005·Current Opinion in Nephrology and Hypertension·Kelly D Smith, Charles E Alpers
Apr 8, 2009·Thrombosis and Haemostasis·Allison A Eddy
Jan 18, 2008·Journal of the American Society of Nephrology : JASN·Sekiko TanedaCharles E Alpers
Apr 25, 2013·Korean journal of urology·Ji Yong LeeChong Koo Sul
Jul 12, 2002·American Journal of Physiology. Renal Physiology·Allison A Eddy

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