Moderately elevated blood pressure during pregnancy and odds of hypertension later in life: the POUCHmoms longitudinal study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/1/bjo14556-sup-0010-ICMJE7.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/2/bjo14556-sup-0007-ICMJE4.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/3/bjo14556.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/4/bjo14556-sup-0008-ICMJE5.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/5/bjo14556-sup-0001-TableS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/6/bjo14556-sup-0002-TableS2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/7/bjo14556-sup-0005-ICMJE2.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/8/bjo14556-sup-0003-TableS3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/9/bjo14556-sup-0006-ICMJE3.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/10/bjo14556-sup-0009-ICMJE6.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/11/bjo14556_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138364/12/bjo14556-sup-0004-ICMJE1.pd

Identification of a Novel Signaling Pathway and Its Relevance for GluA1 Recycling

We previously showed that the serum- and glucocorticoid-inducible kinase 3 (SGK3) increases the AMPA-type glutamate receptor GluA1 protein in the plasma membrane. The activation of AMPA receptors by NMDA-type glutamate receptors eventually leads to postsynaptic neuronal plasticity. Here, we show that SGK3 mRNA is upregulated in the hippocampus of new-born wild type Wistar rats after NMDA receptor activation. We further demonstrate in the Xenopus oocyte expression system that delivery of GluA1 protein to the plasma membrane depends on the small GTPase RAB11. This RAB-dependent GluA1 trafficking requires phosphorylation and activation of phosphoinositol-3-phosphate-5-kinase (PIKfyve) and the generation of PI(3,5)P2. In line with this mechanism we could show PIKfyve mRNA expression in the hippocampus of wild type C57/BL6 mice and phosphorylation of PIKfyve by SGK3. Incubation of hippocampal slices with the PIKfyve inhibitor YM201636 revealed reduced CA1 basal synaptic activity. Furthermore, treatment of primary hippocampal neurons with YM201636 altered the GluA1 expression pattern towards reduced synaptic expression of GluA1. Our findings demonstrate for the first time an involvement of PIKfyve and PI(3,5)P2 in NMDA receptor-triggered synaptic GluA1 trafficking. This new regulatory pathway of GluA1 may contribute to synaptic plasticity and memory

Estrogen Receptor Alpha Is Expressed in Mesenteric Mesothelial Cells and Is Internalized in Caveolae upon Freund's Adjuvant Treatment

Transformation of epithelial cells into connective tissue cells (epithelial-mesenchymal transition, EMT) is a complex mechanism involved in tumor metastasis, and in normal embryogenesis, while type II EMT is mainly associated with inflammatory events and tissue regenaration. In this study we examined type II EMT at the ultrastructural and molecular level during the inflammatory process induced by Freund's adjuvant treatment in rat mesenteric mesothelial cells. We found that upon the inflammatory stimulus mesothelial cells lost contact with the basal lamina and with each other, and were transformed into spindle-shaped cells. These morphological changes were accompanied by release of interleukins IL-1alpha, -1beta and IL-6 and by secretion of transforming growth factor beta (TGF-beta) into the peritoneal cavity. Mesothelial cells also expressed estrogen receptor alpha (ER-alpha) as shown by immunolabeling at the light and electron microscopical levels, as well as by quantitative RT-PCR. The mRNA level of ER-alpha showed an inverse correlation with the secretion of TGF-beta. At the cellular and subcellular levels ER-alpha was colocalized with the coat protein caveolin-1 and was found in the plasma membrane of mesothelial cells, in caveolae close to multivesicular bodies (MVBs) or in the membrane of these organelles, suggesting that ER-alpha is internalized via caveola-mediated endocytosis during inflammation. We found asymmetric, thickened, electron dense areas on the limiting membrane of MVBs (MVB plaques) indicating that these sites may serve as platforms for collecting and organizing regulatory proteins. Our morphological observations and biochemical data can contribute to form a potential model whereby ER-alpha and its caveola-mediated endocytosis might play role in TGF-beta induced type II EMT in vivo

Plasma and cellular fibronectin: distinct and independent functions during tissue repair

Fibronectin (FN) is a ubiquitous extracellular matrix (ECM) glycoprotein that plays vital roles during tissue repair. The plasma form of FN circulates in the blood, and upon tissue injury, is incorporated into fibrin clots to exert effects on platelet function and to mediate hemostasis. Cellular FN is then synthesized and assembled by cells as they migrate into the clot to reconstitute damaged tissue. The assembly of FN into a complex three-dimensional matrix during physiological repair plays a key role not only as a structural scaffold, but also as a regulator of cell function during this stage of tissue repair. FN fibrillogenesis is a complex, stepwise process that is strictly regulated by a multitude of factors. During fibrosis, there is excessive deposition of ECM, of which FN is one of the major components. Aberrant FN-matrix assembly is a major contributing factor to the switch from normal tissue repair to misregulated fibrosis. Understanding the mechanisms involved in FN assembly and how these interplay with cellular, fibrotic and immune responses may reveal targets for the future development of therapies to regulate aberrant tissue-repair processes

Joining S100 proteins and migration:for better or for worse, in sickness and in health

The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins). Finally, we shall attempt to demonstrate how aberrant expression of the S100 proteins may lead to pathological events and human disorders and furthermore provide a rationale to possibly explain why the expression of some of the S100 proteins (mainly S100A4 and S100P) has led to conflicting results on motility, depending on the cells used. © 2013 Springer Basel

Maternal risk of hypertension 7–15 years after pregnancy: clues from the placenta

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/1/bjo16498-sup-0004-ICMJE2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/2/bjo16498-sup-0001-FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/3/bjo16498-sup-0011-ICMJE9.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/4/bjo16498-sup-0008-ICMJE6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/5/bjo16498-sup-0005-ICMJE3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/6/bjo16498-sup-0003-ICMJE1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/7/bjo16498-sup-0010-ICMJE8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/8/bjo16498-sup-0009-ICMJE7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/9/bjo16498_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/10/bjo16498-sup-0006-ICMJE4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/11/bjo16498-sup-0002-FigS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/12/bjo16498.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/167130/13/bjo16498-sup-0007-ICMJE5.pd