Anaplastic Lymphoma Kinase activating mechanisms and signaling pathways

Camici, Marcella; Galetta, Fabio; Abraham, Nader; Carpi, Angelo

doi:10.2741/441

Cited by 10 publications

(3 citation statements)

References 143 publications

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“…Their expression patterns are consistent with our microarray data. Among these genes, proteins encoded by SERPINE1 [ 31] , [32], ANGPT4 [ 33] , [34], DCN [ 35 ], CCL20 [ 36] , [37], IL-1β [ 38] , [39], SPP1 [ 40] , [41] and CCL2 [ 42] , [43] have previously been described to play roles in kidney development or renal disorders including focal segmental glomerulosclerosis (FSGS). By contrast, the role of proteins encoded by NRCAM , GPR56 and MEOX1 have not been directly linked to podocyte function.…”

Section: Resultsmentioning

confidence: 99%

Microarray Analyses of Glucocorticoid and Vitamin D3 Target Genes in Differentiating Cultured Human Podocytes

et al. 2013

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Glomerular podocytes are highly differentiated epithelial cells that are key components of the kidney filtration units. Podocyte damage or loss is the hallmark of nephritic diseases characterized by severe proteinuria. Recent studies implicate that hormones including glucocorticoids (ligand for glucocorticoid receptor) and vitamin D3 (ligand for vitamin D receptor) protect or promote repair of podocytes from injury. In order to elucidate the mechanisms underlying hormone-mediated podocyte-protecting activity from injury, we carried out microarray gene expression studies to identify the target genes and corresponding pathways in response to these hormones during podocyte differentiation. We used immortalized human cultured podocytes (HPCs) as a model system and carried out in vitro differentiation assays followed by dexamethasone (Dex) or vitamin D3 (VD3) treatment. Upon the induction of differentiation, multiple functional categories including cell cycle, organelle dynamics, mitochondrion, apoptosis and cytoskeleton organization were among the most significantly affected. Interestingly, while Dex and VD3 are capable of protecting podocytes from injury, they only share limited target genes and affected pathways. Compared to VD3 treatment, Dex had a broader and greater impact on gene expression profiles. In-depth analyses of Dex altered genes indicate that Dex crosstalks with a broad spectrum of signaling pathways, of which inflammatory responses, cell migration, angiogenesis, NF-κB and TGFβ pathways are predominantly altered. Together, our study provides new information and identifies several new avenues for future investigation of hormone signaling in podocytes.

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Section: Resultsmentioning

confidence: 99%

Microarray Analyses of Glucocorticoid and Vitamin D3 Target Genes in Differentiating Cultured Human Podocytes

et al. 2013

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“…In spite of the absence of histologically evident glomerulopathy, obese mice presented proteinuria, an important sign of glomerular injury. Podocyte dysfunction is related to proteinuria in obese patients [ 28 ] and mice [ 25 ]. Accordingly, we found a downregulation of nephrin and podocin expressions in obese mice kidneys that certainly contributed to podocyte injury and to proteinuria.…”

Section: Discussionmentioning

confidence: 99%

Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice

et al. 2017

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Obesity and its consequences can damage the kidney over time. However, less is known about the impact of developing overweight/obesity during childhood on the kidney in adulthood and the renal impact of a superimposed acute kidney injury (AKI). This study evaluated the effect of obesity induced by a high-fat diet initiated soon after weaning on the adult life of mice and their response to superimposed nephrotoxic effects of cisplatin. C57BL/6 post-weaning mice (3 weeks old) were divided into a control group (CT, n = 12) and a high-fat diet group (HF, n = 12). After 9 weeks, animals were further divided into the following groups: CT, CT treated with a single dose of cisplatin (CTCis, 20 mg/kg, i.p.), HF and HF treated with cisplatin (HFCis). The HF group exhibited higher body weight gain compatible with a moderate obesity. Obese mice presented increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration and proteinuria, without any significant changes in blood pressure and glycemia. AKI induced by cisplatin was exacerbated in obese animals with a 92% reduction in the GFR versus a 31% decrease in the CTCis group; this sharp decline resulted in severely elevated serum creatinine and urea levels. Acute tubular necrosis induced by cisplatin was worsened in obese mice. The HFCis group exhibited robust systemic and intrarenal inflammation that was significantly higher than that in the CTCis group; the HFCis group also showed a higher degree of renal oxidative stress. In conclusion, the moderate degree of obesity induced shortly after weaning resulted in mild early renal alterations, however, obese young animals were prone to develop a much more severe AKI induced by cisplatin.

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“…[ 8 9 ] The structural and functional disruption of podocytes will lead to proteinuria and renal dysfunction in kidney diseases including ORG. [ 10 ] Many studies on patients with ORG and animal model of ORG have illustrated that the podocyte damage was the hallmark of ORG. [ 11 12 ] Now, it is generally recognized that podocyte damage might play a pivotal role in the occurrence and progression of ORG.…”

Section: Introductionmentioning

confidence: 99%

Purinergic 2X7 Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome

Hou

Dong

Sun

et al. 2018

Chinese Medical Journal

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Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding. The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079). The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3, ASC, and caspase-1, as well as the podocyte-associated molecules including nephrin, podocin, and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Western blot analysis, respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo, which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules. Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression of podocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro, and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation of NLRP3 inflammasome, and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

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Anaplastic Lymphoma Kinase activating mechanisms and signaling pathways

Cited by 10 publications

References 143 publications

Microarray Analyses of Glucocorticoid and Vitamin D3 Target Genes in Differentiating Cultured Human Podocytes

Microarray Analyses of Glucocorticoid and Vitamin D3 Target Genes in Differentiating Cultured Human Podocytes

Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice

Purinergic 2X7 Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome

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