Spatial Localization of Collagen Hydroxylated Proline Site Variation as an Ancestral Trait in the Breast Cancer Microenvironment.

Collagen stroma interactions within the extracellular microenvironment of breast tissue play a significant role in breast cancer, including risk, progression, and outcomes. Hydroxylation of proline (HYP) is a common post-translational modification directly linked to breast cancer survival and progression. Changes in HYP status lead to alterations in epithelial cell signaling, extracellular matrix remodeling, and immune cell recruitment.

Gene expression and cellular changes in injured myocardium of .

is an invertebrate animal model system that is well characterized and has many advantages for the study of cardiovascular biology. The regulatory mechanisms of cardiac myocyte proliferation in are intriguing since regeneration of functional tissue has been demonstrated in other organs of in response to injury To identify genes that are differentially expressed in response to cardiac injury, microarray analysis was conducted on RNA from adult hearts with normal or damaged myocardium. After a 24- or 48-h recovery period, total RNA was isolated from damaged and control hearts.

Epicardial deletion of Sox9 leads to myxomatous valve degeneration and identifies Cd109 as a novel gene associated with valve development.

Epicardial-derived cells (EPDCs) are involved in the regulation of myocardial growth and coronary vascularization and are critically important for proper development of the atrioventricular (AV) valves. SOX9 is a transcription factor expressed in a variety of epithelial and mesenchymal cells in the developing heart, including EPDCs. To determine the role of SOX9 in epicardial development, an epicardial-specific Sox9 knockout mouse model was generated.

Complement factor B is essential for the proper function of the peripheral auditory system.

Sensorineural hearing loss is associated with dysfunction of cochlear cells. Although immune cells play a critical role in maintaining the inner ear microenvironment, the precise immune-related molecular mechanisms underlying the pathophysiology of hearing loss remain unclear. The complement cascade contributes to the regulation of immune cell activity.

The Stria Vascularis in Mice and Humans Is an Early Site of Age-Related Cochlear Degeneration, Macrophage Dysfunction, and Inflammation.

Age-related hearing loss, or presbyacusis, is a common degenerative disorder affecting communication and quality of life for millions of older adults. Multiple pathophysiologic manifestations, along with many cellular and molecular alterations, have been linked to presbyacusis; however, the initial events and causal factors have not been clearly established. Comparisons of the transcriptome in the lateral wall (LW) with other cochlear regions in a mouse model (of both sexes) of "normal" age-related hearing loss revealed that early pathophysiological alterations in the stria vascularis (SV) are associated with increased macrophage activation and a molecular signature indicative of inflammaging, a common form of immune dysfunction.

Sfrp4 expression in thyroxine treated calvarial cells.

Aims: Evidence suggests alterations of thyroid hormone levels can disrupt normal bone development. Most data suggest the major targets of thyroid hormones to be the Htra1/Igf1 pathway. Recent discovery by our group suggests involvement of targets WNT pathway, specifically overexpression of antagonist Sfrp4 in the presence of exogenous thyroid hormone.

Two distinct types of nodes of Ranvier support auditory nerve function in the mouse cochlea.

The auditory nerve (AN) of the inner ear is the primary conveyor of acoustic information from sensory hair cells to the brainstem. Approximately 95% of peripheral AN fibers are myelinated by glial cells. The integrity of myelin and the glial-associated paranodal structures at the node of Ranvier is critical for normal AN activity and axonal survival and function in the central auditory nervous system.

PDE5 inhibition rescues mitochondrial dysfunction and angiogenic responses induced by Akt3 inhibition by promotion of PRC expression.

Akt3 regulates mitochondrial content in endothelial cells through the inhibition of PGC-1α nuclear localization and is also required for angiogenesis. However, whether there is a direct link between mitochondrial function and angiogenesis is unknown. Here we show that Akt3 depletion in primary endothelial cells results in decreased uncoupled oxygen consumption, increased fission, decreased membrane potential, and increased expression of the mitochondria-specific protein chaperones, HSP60 and HSP10, suggesting that Akt3 is required for mitochondrial homeostasis.

The acute transcriptome response of the midbrain/diencephalon to injury in the adult mummichog (Fundulus heteroclitus).

Adult fish produce new cells throughout their central nervous system during the course of their lives and maintain a tremendous capacity to repair damaged neural tissue. Much of the focus on understanding brain repair and regeneration in adult fish has been directed at regions of the brainstem and forebrain; however, the mesencephalon (midbrain) and diencephalon have received little attention. We sought to examine differential gene expression in the midbrain/diencephalon in response to injury in the adult fish using RNA-seq.

Age-dependent alterations of Kir4.1 expression in neural crest-derived cells of the mouse and human cochlea.

Age-related hearing loss (or presbyacusis) is a progressive pathophysiological process. This study addressed the hypothesis that degeneration/dysfunction of multiple nonsensory cell types contributes to presbyacusis by evaluating tissues obtained from young and aged CBA/CaJ mouse ears and human temporal bones. Ultrastructural examination and transcriptomic analysis of mouse cochleas revealed age-dependent pathophysiological alterations in 3 types of neural crest-derived cells, namely intermediate cells in the stria vascularis, outer sulcus cells in the cochlear lateral wall, and satellite cells in the spiral ganglion.

Transcriptomic characterization of signaling pathways associated with osteoblastic differentiation of MC-3T3E1 cells.

Bone remodeling involves the coordinated actions of osteoclasts, which resorb the calcified bony matrix, and osteoblasts, which refill erosion pits created by osteoclasts to restore skeletal integrity and adapt to changes in mechanical load. Osteoblasts are derived from pluripotent mesenchymal stem cell precursors, which undergo differentiation under the influence of a host of local and environmental cues. To characterize the autocrine/paracrine signaling networks associated with osteoblast maturation and function, we performed gene network analysis using complementary "agnostic" DNA microarray and "targeted" NanoString nCounter datasets derived from murine MC3T3-E1 cells induced to undergo synchronized osteoblastic differentiation in vitro.

Maternal cardiac messenger RNA expression of extracellular matrix proteins in mice during pregnancy and the postpartum period.

This study provides the first comprehensive analysis of extracellular matrix protein (ECM) gene expression combined with echocardiographic analyses of heart functional parameters in the murine heart during pregnancy and the early postpartum period. Our findings show regulation of all Timp, selected Mmps, and Col1a1, Col3a1, and Col8a1 mRNA levels with reproductive status, with the greatest number of significant changes occurring in the early postpartum period. Left ventricle cardiac diastolic parameters were the first to change during pregnancy and remained elevated postpartum, whereas systolic parameters were increased in late pregnancy and began to recover during the first week postpartum.

Smoking-induced control of miR-133a-3p alters the expression of EGFR and HuR in HPV-infected oropharyngeal cancer.

Purpose: Human papillomavirus (HPV) infected oropharyngeal squamous cell carcinoma (OPSCC) patients have a better prognosis compared to HPV(-) counterparts. However, a subset of HPV(+) patients with a smoking history fail to respond to the standard of care treatments such as radiation and chemotherapy. To understand the underlying mechanism driving HPV(+) OPSCC patient resistance to treatment and recurrence, we sought to identify and characterize the differentially expressed miRNAs and their target genes in HPV(+) smokers and non-smokers.

Noise-Induced Dysregulation of RNA Binding Proteins Contributes to Auditory Nerve Demyelination and Hearing Loss.

Noise exposure causes auditory nerve (AN) degeneration and hearing deficiency, though the proximal biological consequences are not entirely understood. Most AN fibers and spiral ganglion neurons are ensheathed by myelinating glia that provide insulation and ensure rapid transmission of nerve impulses from the cochlea to the brain. Here we show that noise exposure administered to mice of either sex rapidly affects myelinating glial cells, causing molecular and cellular consequences that precede nerve degeneration.

Macrophage-Mediated Glial Cell Elimination in the Postnatal Mouse Cochlea.

Hearing relies on the transmission of auditory information from sensory hair cells (HCs) to the brain through the auditory nerve. This relay of information requires HCs to be innervated by spiral ganglion neurons (SGNs) in an exclusive manner and SGNs to be ensheathed by myelinating and non-myelinating glial cells. In the developing auditory nerve, mistargeted SGN axons are retracted or pruned and excessive cells are cleared in a process referred to as nerve refinement.

Serum Proteins Associated with Emphysema Progression in Severe Alpha-1 Antitrypsin Deficiency.

Computed tomography (CT) lung density is an accepted biomarker for emphysema in alpha-1 antitrypsin deficiency (AATD), although concerns for radiation exposure limit its longitudinal use. Serum proteins associated with emphysema, particularly in early disease, may provide additional pathogenic insights. We investigated whether distinct proteomic signatures characterize the presence and progression of emphysema in individuals with severe AATD and normal forced expiratory volume in 1 second (FEV).

Contributions of Mouse and Human Hematopoietic Cells to Remodeling of the Adult Auditory Nerve After Neuron Loss.

The peripheral auditory nerve (AN) carries sound information from sensory hair cells to the brain. The present study investigated the contribution of mouse and human hematopoietic stem cells (HSCs) to cellular diversity in the AN following the destruction of neuron cell bodies, also known as spiral ganglion neurons (SGNs). Exposure of the adult mouse cochlea to ouabain selectively killed type I SGNs and disrupted the blood-labyrinth barrier.

Expression of V3 Versican by Rat Arterial Smooth Muscle Cells Promotes Differentiated and Anti-inflammatory Phenotypes.

Arterial smooth muscle cells (ASMCs) undergo phenotypic changes during development and pathological processes in vivo and during cell culture in vitro. Our previous studies demonstrated that retrovirally mediated expression of the versican V3 splice variant (V3) by ASMCs retards cell proliferation and migration in vitro and reduces neointimal thickening and macrophage and lipid accumulation in animal models of vascular injury and atherosclerosis. However, the molecular pathways induced by V3 expression that are responsible for these changes are not yet clear.

Fibulin-1 suppresses endothelial to mesenchymal transition in the proximal outflow tract.

Endothelial to mesenchymal transition (EMT) that occurs during cardiac outflow tract (OFT) development is critical for formation of the semilunar valves. Fibulin-1 (Fbln1) is an extracellular matrix protein that is present at several sites of EMT, including the OFT (i.e.

Fibulin-1 is required for bone formation and Bmp-2-mediated induction of Osterix.

The extracellular matrix protein Fibulin-1 (Fbln1) has been shown to be involved in numerous processes including cardiovascular and lung development. Here we have examined the role of Fbln1 in bone formation. Alizarin red staining of skulls from Fbln1-deficient mice showed reduced mineralization of both membranous and endochondral bones.