Department of Laboratory Medicine and Pathology, University of Minnesota, 420 Washington Ave. SE, Minneapolis, MN 55455, USA.
Published: April 2021
AI Article Synopsis
Article Abstract
Pancreatic endocrine cell development is dependent on the rescue of the neurogenin3 (Ngn3) transcription factor from repression by Notch. The signals that prevent Notch signaling, thereby allowing the formation of pancreatic endocrine cells, remain unclear. We show that inhibiting serpinB13, a cathepsin L (CatL) protease inhibitor expressed in the pancreatic epithelium, caused in vitro and in vivo cleavage of the extracellular domain of Notch1. This was followed by a twofold increase in the Ngn3 progenitor cell population and enhanced conversion of these cells to express insulin. Conversely, both recombinant serpinB13 protein and CatL deficiency down-regulated pancreatic Ngn3 cell output. Mouse embryonic exposure to inhibitory anti-serpinB13 antibody resulted in increased islet cell mass and improved outcomes in streptozotocin-induced diabetes at 8 weeks of age. Moreover, anti-serpinB13 autoantibodies stimulated Ngn3 endocrine progenitor formation in the pancreas and were associated with delayed progression to type 1 diabetes (T1D) in children. These data demonstrate long-term impact of serpinB13 activity on islet biology and suggest that promoting protease activity by blocking this serpin may have prophylactic potential in T1D.
Research towards regenerative dentistry focused on developing scaffold materials whose high performance induces cell adhesion support and guides tissue growth. An early study investigated the proliferation abilities and attachment of human periodontal ligament fibroblasts (HPLFs) on two bovine pericardium membranes with different thicknesses, 0.2 mm and 0.
Aims: This study aimed to explore the role and underlying mechanisms of brain-derived exosomes in traumatic brain injury-induced acute lung injury (TBI-induced ALI), with a particular focus on the potential regulation of ferroptosis through miRNAs and Scd1.
Methods: To elucidate TBI-induced ALI, we used a TBI mouse model. Exosomes were isolated from the brains of these mice and characterized using TEM and NTA.
Background: Hypertension or elevated blood pressure (BP) is a worldwide clinical challenge and the leading primary risk factor for kidney dysfunctions, heart failure, and cerebrovascular disease. The kidney is a central regulator of BP by maintaining sodium-water balance. Multiple genome-wide association studies revealed that BP is a heritable quantitative trait, modulated by several genetic, epigenetic, and environmental factors.
Background: Women who had preeclampsia (a history of preeclampsia) have a >4-fold risk of developing cardiovascular disease compared with women who had an uncomplicated pregnancy (history of healthy pregnancy). Despite the remission of clinical symptoms after pregnancy, vascular endothelial dysfunction persists postpartum, mediated in part by exaggerated Ang II (angiotensin II)-mediated constriction. However, the role of vasodilatory ATRs (Ang II type 2 receptors) in this dysfunction is unknown.
Aggregates of two mouse embryos produce viable offspring of normal size, indicating that there are mechanisms in the embryo that can downregulate their size to the size of the corresponding normal (single) embryos. Very little is known about the mechanisms controlling compensation for increased preimplantation size. Also, it is still elusive when exactly during development chimeric embryos regulate their size.
