title: Mesangial cell apoptosis induced by a fibronectin fragment.
abstract: We previously showed that in passive Heymann nephritis (PHN) rats, a large quantity of fibronectin (FN) fragments containing the central cell-binding (CCB) domain and adjacent domains are generated in the kidney and excreted into urine (Nishizawa et al., Biol Pharm Bull 1998; 21: 429-433). To ascertain whether the FN fragments could affect the progression of PHN, we investigated the effect of a 150 K FN fragment containing the CCB and carboxyl-terminal heparin-binding (Hep 2) domains on cultured rat mesangial cells. When rat mesangial cells cultured on FN-coated plates were exposed to the 150 K FN fragment, some mesangial cells detached from the FN substrate and then underwent apoptosis as judged by nuclear and DNA fragmentations. The 150 K FN fragment competitively inhibited the mesangial cell adhesion to the FN substrate in a dose-dependent manner. Furthermore, gelatinzymography of the conditioned medium of mesangial cells showed that the 150 K FN fragment induced and/or potentiated the extracellular matrix (ECM)-degrading proteinases including matrix metalloproteinases (MMPs) of mesangial cells. These results indicate that the 150 K FN fragment may elicit mesangial cell apoptosis by disrupting the mesangial cell adhesion through two distinct ways: the inhibition of mesangial cell adhesion and the ECM-degradation by the 150 K FN fragment-induced MMPs. Thus, FN fragments containing the CCB and adjacent domains generated in the kidneys of PHN rats may be involved in the evolution of the renal injury.
authors.affiliation: Department of Patho-Physiology, Faculty of Pharmaceutical Sciences, Science University of Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Nishizawa
authors.forename: F
authors.initials: F
authors.lastname: Fukai
authors.forename: Y
authors.initials: Y
authors.lastname: Natori
authors.forename: R
authors.initials: R
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Tanuma
authors.forename: T
authors.initials: T
authors.lastname: Katayama