Effect of chlorpromazine on kinetics of injected monoclonal antibody in MoAb-induced glomerular injury

Takashima, N; Kawachi, Hiroshi; Oite, Takashi; Nishi, S; Arakawa, Masaaki; Shimizu, Fujio

doi:10.1111/j.1365-2249.1993.tb03368.x

Cited by 8 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we concluded that mAb 5‐1‐6 identifies the extracellular domain of nephrin, 25,26 which documented the importance of the slit diaphragm and its component, nephrin, in the regulation of glomerular permselectivity. We have already reported some investigations of the pathogenesis of mAb 5‐1‐6 nephropathy 5,24 , 27–30 and investigations of the expression of mAb 5‐1‐6 antigen in the proteinuric states 31,32 and in the developing glomeruli 33,34 . All of our observations on the expression of mAb 5‐1‐6 antigen reported previously should be interpreted as observations on the expression of nephrin.…”

Section: Barrier Function Of the Slit Diaphragmsupporting

confidence: 59%

Role of podocyte slit diaphragm as a filtration barrier (Review Article)

et al. 2006

View full text Add to dashboard Cite

Although the role of glomerular basement membrane has been emphasised as the barrier for retaining plasma proteins in the past three decades, some recent studies have demonstrated that the slit diaphragm of the glomerular epithelial cell (podocyte) is the structure likely to be the barrier in the glomerular capillary wall. Nephrin and podocin were identified as gene products mutated in Finnish-type congenital nephrotic syndrome and autosomal recessive steroid-resistant nephrotic syndrome, respectively. Nephrin s located at the outer leaflet of plasma membranes of the slit diaphragm. Podocin is reported to have an interaction with nephrin. The anti-nephrin antibody is capable of inducing massive proteinuria, which indicates that nephrin is a key functional molecule in the slit diaphragm. The expression of nephrin and podocin was reduced in glomeruli of minimal change nephrotic syndrome, which suggested that the altered expression of these molecules contributes to the development of proteinuria also in acquired diseases. Some recent studies demonstrated that CD2-associated protein (CD2AP) is also a functional molecule in the slit diaphragm, and its expression is altered in membranous nephropathy. These observations suggested that alteration of the molecular arrangement in the slit diaphragm is involved in the development of proteinuria in several kinds of glomerular diseases.

show abstract

Section: Barrier Function Of the Slit Diaphragmsupporting

confidence: 59%

Role of podocyte slit diaphragm as a filtration barrier (Review Article)

et al. 2006

View full text Add to dashboard Cite

show abstract

mAb 5‐1‐6 nephropathy and nephrin

Kawachi

Koike

Shimizu

2002

Microscopy Res & Technique

View full text Add to dashboard Cite

It is well established that the glomerular capillary wall consists of three layers: endothelial cell, glomerular basement membrane, and the slit diaphragm bridging foot processes of glomerular epithelial cell. Which structure in the glomerular capillary wall represents the primary filter for retaining plasma proteins is not clearly elucidated. An anti-slit diaphragm monoclonal antibody (mAb) 5-1-6 causes massive proteinuria in rats by single intravenous injection, which clearly indicates that the slit diaphragm plays a critical role for maintaining the barrier function of the glomerular capillary wall. Recently, we concluded that mAb 5-1-6 recognized a rat homolog of nephrin, a gene product of NPHS1. The expression of nephrin decreased in puromycin aminonucleoside nephropathy and adriamycin nephropathy as well as mAb 5-1-6-induced nephropathy, which suggested that nephrin was involved in the development of proteinuria in these proteinuric states. In mAb 5-1-6 nephropathy, the slit diaphragm was maintained morphologically normal, although nephrin expression dramatically decreased. The finding suggested that nephrin was not a sole component of the slit diaphragm. To better understand the structure of the slit diaphragm, it is particularly important to identify other components that build up the structure of the slit diaphragm together with nephrin.

show abstract

Transient myofibroblast differentiation of interstitial fibroblastic cells relevant to tubular dilatation in uranyl acetate-induced acute renal failure in rats

et al. 2004

View full text Add to dashboard Cite

To investigate the mechanisms of myofibroblast differentiation of interstitial fibroblastic cells (FCs) in rats with uranyl acetate-induced acute renal failure (ARF), we examined the relationship between the expression of alpha-smooth muscle actin (alpha-SMA), myofibroblast phenotype and tubular dilatation as well as cell shape and adhesion of FCs. Peritubular alpha-SMA-positive myofibroblasts appeared after induction of ARF and extended along the damaged, dilated proximal tubules and then almost disappeared after proximal tubular recovery. The perimeter of proximal tubules correlated with fractional areas stained for alpha-SMA (P<0.001). Most alpha-SMA-positive cells did not incorporate [3H]-thymidine, indicating a low proliferative activity. Transmission electron microscopy showed that FCs increasingly attached to the tubular basement membrane by elongated cytoplasm-containing microfilament bundles, which formed abundant adherens and gap junctions from day 4 to day 7. Scanning electron microscopy showed hypertrophic FCs covering large areas of tubules after induction of ARF. Administration of chlorpromazine, which can inhibit cytoskeletal movement, after induction of ARF partially inhibited myofibroblast differentiation of FCs immunohistochemically and morphologically and resulted in more dilated proximal tubules in concert with aggravation of renal dysfunction and inhibition of regenerative repair at day 4 than vehicle-administered rats. Our results indicate that mechanical tension, judged by tubular dilatation, may contribute to the induction of alpha-SMA phenotype with increased stress fiber formation and intercellular junctions in FCs to support damaged nephron structures by adjusting tensional homeostasis in rats with uranyl acetate-induced ARF.

show abstract

Effect of chlorpromazine on kinetics of injected monoclonal antibody in MoAb-induced glomerular injury

Cited by 8 publications

References 16 publications

Role of podocyte slit diaphragm as a filtration barrier (Review Article)

Role of podocyte slit diaphragm as a filtration barrier (Review Article)

mAb 5‐1‐6 nephropathy and nephrin

Transient myofibroblast differentiation of interstitial fibroblastic cells relevant to tubular dilatation in uranyl acetate-induced acute renal failure in rats

Contact Info

Product

Resources

About