| 1. |
- Liu, Peidi, 1986, et al.
(author)
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Transcriptomic and Proteomic Profiling Provides Insight into Mesangial Cell Function in IgA Nephropathy
- 2017
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In: Journal of the American Society of Nephrology. - : Ovid Technologies (Wolters Kluwer Health). - 1046-6673 .- 1533-3450. ; 28:10, s. 2961-2972
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Journal article (peer-reviewed)abstract
- IgA nephropathy (IgAN), the most common GN worldwide, is characterized by circulating galactose-deficient IgA (gd-IgA) that forms immune complexes. The immune complexes are deposited in the glomerular mesangium, leading to inflammation and loss of renal function, but the complete pathophysiology of the disease is not understood. Using an integrated global transcriptomic and proteomic profiling approach, we investigated the role of the mesangium in the onset and progression of IgAN. Global gene expression was investigated by microarray analysis of the glomerular compartment of renal biopsy specimens from patients with IgAN (n=19) and controls (n=22). Using curated glomerular cell type specific genes from the published literature, we found differential expression of a much higher percentage of mesangial cell positive standard genes than podocyte-positive standard genes in IgAN. Principal coordinate analysis of expression data revealed clear separation of patient and control samples on the basis of mesangial but not podocyte cell positive standard genes. Additionally, patient clinical parameters (serum creatinine values and eGFRs) significantly correlated with Z scores derived from the expression profile of mesangial cell positive standard genes. Among patients grouped according to Oxford MEST score, patients with segmental glomerulosclerosis had a significantly higher mesangial cell positive standard gene Z score than patients without segmental glomerulosclerosis. By investigating mesangial cell proteomics and glomerular transcriptomics, we identified 22 common pathways induced in mesangial cells by gd-IgA, most of which mediate inflammation. The genes, proteins, and corresponding pathways identified provide novel insights into the pathophysiologic mechanisms leading to IgAN.
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| 2. |
- Ebefors, Kerstin, 1977, et al.
(author)
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Endothelin receptor-A mediates degradation of the glomerular endothelial surface layer via pathologic crosstalk between activated podocytes and glomerular endothelial cells
- 2019
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In: Kidney International. - : Elsevier BV. - 0085-2538. ; 96:4, s. 957-970
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Journal article (peer-reviewed)abstract
- Emerging evidence of crosstalk between glomerular cells in pathological settings provides opportunities for novel therapeutic discovery. Here we investigated underlying mechanisms of early events leading to filtration barrier defects of podocyte and glomerular endothelial cell crosstalk in the mouse models of primary podocytopathy (podocyte specific transforming growth factor-beta receptor 1 signaling activation) or Adriamycin nephropathy. We found that glomerular endothelial surface layer degradation and albuminuria preceded podocyte foot process effacement. These abnormalities were prevented by endothelin receptor-A antagonism and mitochondria! reactive oxygen species scavenging. Additional studies confirmed increased heparanase and hyaluronoglucosaminidase gene expression in glomerular endothelial cells in response to podocyte-released factors and to endothelin-1. Atomic force microscopy measurements showed a significant reduction in the endothelial surface layer by endothelin-1 and podocyte-released factors, which could be prevented by endothelin receptor-A but not endothelin receptor-B antagonism. Thus, our studies provide evidence of early crosstalk between activated podocytes and glomerular endothelial cells resulting in loss of endothelial surface layer, glomerular endothelial cell injury and albuminuria. Hence, activation of endothelin-1-endothelin receptor-A and mitochondrial reactive oxygen species contribute to the pathogenesis of primary podocytopathies in experimental focal segmental glomerulosclerosis.
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| 3. |
- Granqvist, Anna, et al.
(author)
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Podocyte proteoglycan synthesis is involved in the development of nephrotic syndrome
- 2006
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In: Am J Physiol Renal Physiol. - : American Physiological Society. - 0363-6127 .- 1931-857X .- 1522-1466. ; 291
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Journal article (peer-reviewed)abstract
- Proteoglycans (PG) are important for the glomerular barrier, for cell signaling and for the anchorage of cells to the glomerular basement membrane. They are, however, complex macromolecules, and their production has not yet been thoroughly investigated for podocytes. In the present study, we have studied the biosynthesis of proteoglycans by highly differentiated human podocytes and in rats. The cells were treated with puromycin aminonucleoside (PAN, a nephrosis inducing agent), steroids (used as primary treatment for nephrotic syndrome) or both. Analysis was made by Taqman(R)real-time PCR, Western blot and by metabolic labeling with (35)S and (3)H. We found that podocytes produce versican, syndecan-1, decorin and biglycan together with the previously known PGs syndecan-4, glypican and perlecan. PAN treatment down-regulated the mRNA and the protein expression of both versican (by 24+/-6%, p<0.01, for mRNA and by 50% for protein) and perlecan (by 14+/-5%, p<0.05, for mRNA and by 50% for protein). The decreased expression was confirmed by studying the glomerular gene expression in rats treated with PAN during a time course study. In addition, puromycin decreased the expression of enzymes involved in the glycosaminoglycan (GAG) biosynthesis. Steroid treatment decreased perlecan (by 24+/-3%, p<0.01) and syndecan-1 expression (by 30+/-4%, p<0.01), but increased the expression of decorin 2.5-fold. The observed alterations of proteoglycan synthesis induced by PAN may lead to decreased glomerular anionic charge and disturbed podocyte morphology, factors that are important for the development of a nephrotic syndrome.
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| 4. |
- Nordgren, Kenneth, 1962-, et al.
(author)
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Rektorers uppfattningar om undervisningens villkor och en skola på vetenskaplig grund : En uppföljande enkätstudie till undersökningen Lärares planering och efterarbete av lektioner: Infrastrukturer för kollegialt samarbete och forskningssamverkan
- 2022
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Reports (peer-reviewed)abstract
- Föreliggande rapport redovisar resultat från en enkätstudie som riktades till rektorer på grundskola och gymnasium. Undersökningen genomfördes under hösten 2019 inom ramen för ULF (Utbildning, Lärande, Forskning), som är en nationell försöksverksamhet. Målet med försöksverksamheten är att utveckla och pröva hållbara samverkansmodeller mellan akademi och skola vad gäller forskning, skolverksamhet och lärarutbildning.Enkätstudien syftar till att undersöka om kollegial samverkan runt planering och efterarbete kan utgöra en grund för skolutveckling och forskningssamverkan mellan skola och akademi. Enkäten efterfrågade även hur rektorer ser på forskningens roll i skolan. I rapporten sätts resultat från rektorsenkäten även i relation till en lärarenkät genomförd 2018 (Nordgren et al., 2019).Våra studier visar att kollegial samplanering runt undervisning skulle kunna vara central för en samverkan om forskning och utveckling. Resultaten påvisar emellertid stora skillnader mellan hur rektorer och lärare uppfattar villkoren för, och organisationen av utvecklingsarbetet runt undervisning. Ett annat centralt resultat är att rektorer och lärare visar sig intresserade av forskning och samverkan mellan skola och akademi, men båda grupperna ger uttryck för att deras villkor att systematiskt utveckla sin verksamhet är begränsade.Denna rapport ger ett omfattande och rikt underlag för lärare, rektorer, forskare och skolpolitiker att reflektera över vilka strategier som kan vara långsiktiga och hållbara för att understödja en skola på vetenskaplig grund.
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