scholarly journals Apoptosis as a mechanism of the albumin-induced kidney damage in childhood nephrotic syndrome

2018 ◽  
pp. 25-30
Author(s):  
Ie.A. Burlaka ◽  
I.V. Bagdasarova
Keyword(s):  
Nephrotic Syndrome ◽  
Primary Culture ◽  
Kidney Damage ◽  
In Vitro Studies ◽  
Kidney Cells ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Nephrotic Children

It was shown previously on in vivo studies that proteinuria-induced effects play a crucial role in renal damage in chronic kidney disease (CKD). However, an initial mechanism of irreversible kidney damage in pediatric diseases characterized by chronic proteinuria, i.e. nephrotic syndrome, remains to be unclear. The aim of our work was to study the initial mechanism of kidney cells apoptosis development in nephrotic children. Methods.An examination of renal biopsies of 53 patients (aged 10 to 15 years) with nephrotic syndrome hospitalized in Pediatric Nephrology unit of the Children Clinical Hospital №7 (Kyiv, Ukraine) done. In vitro studies of albumin toxicity performed on rat proximal tubular cells in primary culture (RPTC). Results. Our study showed that albumin overload in nephrotic children leads to high levels of apoptosis. Its distribution and level varies regarding the level of focal segmental glomerulosclerosis (FSGS). The progression of sclerosis as a sign of irreversible kidney damage is accompanied by gradual increase in expression of proapoptotic factor Bax. In vitro studies on rat proximal tubular cells in primary culture (RPTC) showed that excessive albumin uptake into rat primary renal cells causes an almost immediate mitochondrial accumulation of the apoptotic factor Bax. We hypothesize that this might be initial pathway leading to kidney cells apoptosis in childhood nephrotic syndrome. Conclusions. We show thatoverexpression of apoptotic factor Bax has a place in children with nephrotic syndrome. Thus, chronic influence of albumin is a factor predisposing disturbances in system controlling apoptosis in this cohort of patients. Our data demonstrate that there is a dependence between the Bax overexpression level and the stage of CKD. We show the topologic difference between the Bax levels and FSGS degree. This is an indication thatdevelopment of glomerular and tubule-interstitial disorders under the influence of proteinuria occurs in specific range. In vitro data demonstrate that albumin overload causes mitochondrial Bax translocation that could be an initial factor in apoptotic pathway activation.

Isolation and Culture of Proximal Tubular Cells from Porcine Kidney

1993 ◽  
Vol 21 (4) ◽  
pp. 457-465
Author(s):  
Marieke Kruidering ◽  
Frans A. Prins ◽  
Emile de Heer ◽  
Gerard J. Mulder ◽  
J. Fred Nagelkerke
Keyword(s):  
Primary Culture ◽  
Single Cells ◽  
Proximal Tubular Cells ◽  
Isolated Cells ◽  
Serum Free ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Vitro Model ◽  
Serum Free Conditions

Porcine proximal tubular cells (PPTC) were isolated from kidneys obtained from slaughterhouse pigs. After disruption of the connective tissue by collagenase, purification was achieved by filtration and centrifugation on a discontinuous density gradient. Single cells and clusters of 10–40 cells were obtained, having a viability of 93–99%. More than 81% of the single cells showed γ-glutamyltranspeptidase (GGT) activity and more than 95% showed non-specific esterase (NE) activity, marker enzymes for proximal tubule cells. One kidney yielded 1 x 107 single cells and 3x107 cells in clusters. Cells were kept in primary culture on plastic or collagen-coated dishes. In the presence of 10% serum, confluency was reached within four days. The monolayers could be kept in culture for four days after confluency, in serum-free conditions. When seeded in serum-free conditions, PPTC did not reach confluency, but the cells could be kept in culture for at least 16 days. The cells displayed epithelial morphology, i.e. cobblestone shape, dome formation, microvilli, basal infoldings and abundant mitochondria. PPTC in primary culture still displayed NE activity, while 80% of the cells showed GGT activity. In conclusion, the isolated cells are of proximal tubular origin, reach confluency in 3–4 days in the presence of 10% serum, and can be kept as monolayers in serum-free conditions for four additional days and may provide a suitable in vitro model for long-term nephrotoxicity studies.

Primary culture of proximal tubular cells from normal rat kidney as an in vitro model to study mechanisms of nephrotoxicity

1990 ◽  
Vol 39 (8) ◽  
pp. 1335-1345 ◽  
Author(s):  
Pieter J. Boogaard ◽  
J.Paul Zoeteweij ◽  
Theo J.C. Van Berkel ◽  
Joost M. Van't Noordende ◽  
Gerard J. Mulder ◽  
...  
Keyword(s):  
Primary Culture ◽  
In Vitro Model ◽  
Rat Kidney ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Normal Rat ◽  
Vitro Model

In vitro studies of aquaporins 1 and 3 expression in cultured human proximal tubular cells: Upregulation by transferrin but not albumin

2001 ◽  
Vol 38 (2) ◽  
pp. 317-330 ◽  
Author(s):  
Sydney Tang ◽  
Joseph C.K. Leung ◽  
Christopher W.K. Lam ◽  
Fernand Mac-Moune Lai ◽  
Tak Mao Chan ◽  
...  
Keyword(s):  
In Vitro Studies ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

scholarly journals Palmitate aggravates proteinuria-induced cell death and inflammation via CD36-inflammasome axis in the proximal tubular cells of obese mice

2018 ◽  
Vol 315 (6) ◽  
pp. F1720-F1731 ◽  
Author(s):  
Lung-Chih Li ◽  
Jenq-Lin Yang ◽  
Wen-Chin Lee ◽  
Jin-Bor Chen ◽  
Chien-Te Lee ◽  
...  
Keyword(s):  
Cell Death ◽  
Tubular Injury ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Caspase 1 ◽  
Proximal Tubular ◽  
Renal Tubular ◽  
Nlrp3 Inflammasomes

High levels of serum free fatty acids (FFAs) and proteinuria have been implicated in the pathogenesis of obesity-related nephropathy. CD36, a class B scavenger receptor, is highly expressed in the renal proximal tubules and mediates FFA uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation. In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA-induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL/6 mice and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro models. Immunohistochemical staining showed that CD36, IL-1β, and IL-18 levels increased progressively in the kidneys of HFD-fed mice. Sulfo- N-succinimidyl oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3, IL-1β, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL-1β, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment with SSO and the knockdown of caspase-1 expression by siRNA both inhibited palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate causes renal tubular inflammation, cell death, and apoptosis via the CD36/NLRP3/caspase-1 axis, which may explain, at least in part, the mechanism underlying FFA-related renal tubular injury. The blockade of CD36-induced cellular processes is therefore a promising strategy for treating obesity-related nephropathy.

scholarly journals The effect of proteinuria-mediated endothelin-1 downregulation of PKCα signalling in proximal tubular cells and its successful/INS; treatment is measurable using microRNA15a as biomarker in vitro and in vivo

Life Sciences ◽  
2013 ◽  
Vol 93 (25-26) ◽  
pp. e5-e6
Author(s):  
Heike Loeser ◽  
Melanie von Brandenstein ◽  
Maike Wittersheim ◽  
Volker Burst ◽  
Claudia Richter ◽  
...  
Keyword(s):  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Endothelin 1 ◽  
Proximal Tubular
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