Glomerular mRNA Expression of Prothrombotic and Antithrombotic Factors in Renal Transplants With Thrombotic Microangiopathy

Agustian, Putri A.; Bockmeyer, Clemens L.; Modde, Friedrich; Wittig, Juliane; Heinemann, Falko M.; Brundiers, Stephanie; Dämmrich, Maximilian Ernst; Schwarz, Anke; Birschmann, Ingvíld; Suwelack, Barbara; Jindra, Peter T.; Ahlenstiel, Thurid; Wohlschläger, J.; Vester, Udo; Ganzenmüller, Tina; Zilian, Eva; Feldkamp, Thorsten; Spieker, Tilmann; Immenschuh, Stephan; Kreipe, Hans; Bröcker, Verena; Becker, Jan U.

doi:10.1097/tp.0b013e318291a298

Cited by 17 publications

(16 citation statements)

References 43 publications

(35 reference statements)

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“…Based on these diverse roles, loss of Klf2 expression has been implicated in atherosclerosis and thrombotic angiopathy (Agustian et al, 2013;Atkins et al, 2008;Boon et al, 2011). Furthermore, the pleiotropic effects of statins in preventing atherosclerosis might be directly mediated by KLF2 in endothelial cells (Tuuminen et al, 2013).…”

Section: Klfs In Hematopoietic Disordersmentioning

confidence: 99%

Krüppel-like factors in mammalian stem cells and development

2017

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Krüppel-like factors (KLFs) are a family of zinc-finger transcription factors that are found in many species. Recent studies have shown that KLFs play a fundamental role in regulating diverse biological processes such as cell proliferation, differentiation, development and regeneration. Of note, several KLFs are also crucial for maintaining pluripotency and, hence, have been linked to reprogramming and regenerative medicine approaches. Here, we review the crucial functions of KLFs in mammalian embryogenesis, stem cell biology and regeneration, as revealed by studies of animal models. We also highlight how KLFs have been implicated in human diseases and outline potential avenues for future research.

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Section: Klfs In Hematopoietic Disordersmentioning

confidence: 99%

Krüppel-like factors in mammalian stem cells and development

2017

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“…This zinc finger family of transcription factors is important in regulating cellular processes in the vasculature, including the kidney's glomerular capillary bed [33]. For example, in renal transplants with thrombotic microangiopathy, studies of gene expression in the glomerulus have demonstrated a downregulation of KLF2 and subsequent upregulation of genes that inhibit local fibrinolysis [34]. Recently, researchers have shown that the impact of blood flow and its laminar shear stress on glomerular endothelial cells alters expression of KLF2 .…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Markers of Renal Function in African Americans

Bomotti

Smith

Zagel

et al. 2013

Nursing Research and Practice

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Chronic kidney disease (CKD) is an increasing concern in the United States due to its rapidly rising prevalence, particularly among African Americans. Epigenetic DNA methylation markers are becoming important biomarkers of chronic diseases such as CKD. To better understand how these methylation markers play a role in kidney function, we measured 26,428 DNA methylation sites in 972 African Americans from the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We then evaluated (1) whether epigenetic markers are associated with estimated glomerular filtration rate (eGFR), (2) whether the significantly associated markers are also associated with traditional risk factors and/or novel biomarkers for eGFR, and (3) how much additional variation in eGFR is explained by epigenetic markers beyond established risk factors and biomarkers. The majority of methylation markers most significantly associated with eGFR (24 out of the top 30) appeared to function, at least in part, through pathways related to aging, inflammation, or cholesterol. However, six epigenetic markers were still able to significantly predict eGFR after adjustment for other risk factors. This work shows that epigenetic markers may offer valuable new insight into the complex pathophysiology of CKD in African Americans.

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“…RNA was quantified as described previously1314. Briefly, isolated RNA was dissolved in 10 μl DEPC water.…”

Section: Methodsmentioning

confidence: 99%

Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy

Bockmeyer

Säuberlich

Wittig

et al. 2016

Sci Rep

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Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5). Laser-microdissected glomeruli were used for expression profiling of 762 miRNAs by low-density TaqMan arrays (cards A and B). The comparison of different normalization methods (GeNormPlus, NormFinder, global mean and snoRNAs) in crescentic IgA-GN, IgA-GN and controls yielded similar results. However, levels of significance and the range of relative expression differed. In median, two normalization methods demonstrated similar results. GeNormPlus and NormFinder gave different top ranked reference miRNAs. Stability ranking for snoRNAs varied between cards A and B. In conclusion, we suggest the geometric mean of the most stable reference miRNAs found in GeNormPlus (miR-26b-5p), NormFinder (miR-28-5p) and snoRNAs (RNU44) as reference. It should be considered that significant differences could be missed using one particular normalization method. As a starting point for glomerular miRNA studies in IgA nephropathy we provide a library of miRNAs.

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Glomerular mRNA Expression of Prothrombotic and Antithrombotic Factors in Renal Transplants With Thrombotic Microangiopathy

Cited by 17 publications

References 43 publications

Krüppel-like factors in mammalian stem cells and development

Krüppel-like factors in mammalian stem cells and development

Epigenetic Markers of Renal Function in African Americans

Comparison of different normalization strategies for the analysis of glomerular microRNAs in IgA nephropathy

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