An Interspecies Heart-to-Heart: Using Xenopus to Uncover the Genetic Basis of Congenital Heart Disease
AbstractPurpose of ReviewGiven the enormous impact congenital heart disease has on child health, it is imperative that we improve our understanding of the disease mechanisms that underlie patient phenotypes and clinical outcomes. This review will outline the merits of using the frog model,Xenopus, as a tool to study human cardiac development and left-right patterning mechanisms associated with congenital heart disease.Recent FindingsPatient-driven gene discovery continues to provide new insight into the mechanisms of congenital heart disease, and by extension, patient phenotypes and outcomes. By identifying gene variants i...
Source: Current Pathobiology Reports - May 6, 2017 Category: Laboratory Medicine Source Type: research
Using Zebrafish to Model Liver Diseases-Where Do We Stand?
AbstractPurpose of reviewThe liver is the largest internal organ and performs both exocrine and endocrine function that is necessary for survival. Liver failure is among the leading causes of death and represents a major global health burden. Liver transplantation is the only effective treatment for end-stage liver diseases. Animal models advance our understanding of liver disease etiology and hold promise for the development of alternative therapies. Zebrafish has become an increasingly popular system for modeling liver diseases and complements the rodent models.Recent findingsThe zebrafish liver contains main cell types ...
Source: Current Pathobiology Reports - May 3, 2017 Category: Laboratory Medicine Source Type: research
Heterogeneity of Fibroblasts and Myofibroblasts in Pulmonary Fibrosis
AbstractPurpose of ReviewIdiopathic pulmonary fibrosis (IPF) is the most common form of interstitial lung disease of unknown etiopathogenesis with mean survival of 3 –5 years and limited therapeutics. IPF is characterized by a loss of alveolar type II epithelial cells and aberrant activation of stromal cells, leading to a considerable effort to characterize the origin and activation mechanisms of fibroblasts and myofibroblasts in IPF lungs. In this review, th e origin and contribution of fibroblast and myofibroblasts in lung fibrosis will be summarized.Recent FindingsLineage tracing experiments suggested that interstiti...
Source: Current Pathobiology Reports - May 2, 2017 Category: Laboratory Medicine Source Type: research
Mitophagy and Mitochondrial Quality Control Mechanisms in the Heart
AbstractPurpose of ReviewMitochondrial homeostasis and quality control are essential to maintenance of cardiac function and a disruption of this pathway can lead to deleterious cardiac consequences.Recent FindingsMitochondrial quality control has been described as a major homeostatic mechanism in the cell. Recent studies highlighted that an impairment of mitochondrial quality control in different cell or mouse models is linked to cardiac dysfunction. Moreover, some conditions as aging, genetic mutations, or obesity have been associated with mitochondrial quality control alteration leading to an accumulation of damaged mito...
Source: Current Pathobiology Reports - May 2, 2017 Category: Laboratory Medicine Source Type: research
Developmental Signaling and Organ Fibrosis
AbstractPurpose of ReviewRecent evidence suggests that the developmental signaling pathways —Wnt, Notch, and Hedgehog—are critically involved in organ fibrosis.Recent FindingsWnt, Notch, and Hedgehog signaling pathways are reactivated after organ injury and drive pathologic organ fibrosis via myofibroblast differentiation, proliferation, and extracellular matrix production. Strong evidence suggests that inhibition of these pathways might ameliorate fibrosis severity. Some conflicting results point towards highly time- and cell-specific roles of these pathways across major organs.SummaryUsually quiescent in adult tissue...
Source: Current Pathobiology Reports - April 29, 2017 Category: Laboratory Medicine Source Type: research
Matricellular Proteins and Organ Fibrosis
AbstractPurpose of ReviewThis review intends to outline the novel findings on the effects of matricellular proteins in the development of organ fibrosis and present recent advances towards a potential usage of matricellular proteins as markers or targets of therapy for fibrotic diseases.Recent FindingsRecent studies elucidated the sites of production of different matricellular proteins during fibrosis of several organs, their specific binding receptors, and their effects on different cell types. For some proteins, a differential function between chronic disease and acute injury and a connection to regulation of inflammator...
Source: Current Pathobiology Reports - April 28, 2017 Category: Laboratory Medicine Source Type: research
Development Aspects of Zebrafish Myotendinous Junction: a Model System for Understanding Muscle Basement Membrane Formation and Failure
AbstractPurpose of ReviewThe muscle is separated from tendons by a specialised basement membrane that acts as the structural interface of the myotendinous junction (MTJ). In zebrafish, the larval MTJ forms at the vertical myosepta, which separate the individual myomeres that arise during somitogenesis. In this review, we examine the formation of the vertical myosepta in zebrafish. We then describe insights this gains us in the context of muscle basement membrane failure, the mechanistic basis of the inherited muscle wasting condition muscular dystrophy (MD).Recent FindingsWe examine recent manuscripts that investigate how ...
Source: Current Pathobiology Reports - April 28, 2017 Category: Laboratory Medicine Source Type: research
Lung Organoids and Their Use To Study Cell-Cell Interaction
AbstractPurpose of ReviewThe lung research field has pioneered the use of organoids for the study of cell-cell interactions.Recent FindingsThe use of organoids for airway basal cells is routine. However, the development of organoids for the other regions of the lung is still in its infancy. Such cultures usually rely on cell-cell interactions between the stem cells and a putative niche cell for their growth and differentiation.SummaryThe use of co-culture organoid systems has facilitated the in vitro cultivation of previously inaccessible stem cell populations, providing a novel method for dissecting the molecular requirem...
Source: Current Pathobiology Reports - April 24, 2017 Category: Laboratory Medicine Source Type: research
Matricellular Proteins and Organ Fibrosis
AbstractPurpose of ReviewThis review intends to outline the novel findings on the effects of matricellular proteins in the development of organ fibrosis and present recent advances towards a potential usage of matricellular proteins as markers or targets of therapy for fibrotic diseases.Recent FindingsRecent studies elucidated the sites of production of different matricellular proteins during fibrosis of several organs, their specific binding receptors, and their effects on different cell types. For some proteins, a differential function between chronic disease and acute injury and a connection to regulation of inflammator...
Source: Current Pathobiology Reports - April 22, 2017 Category: Laboratory Medicine Source Type: research
Mechanisms of Fibroblast Activation in the Remodeling Myocardium
AbstractPurpose of ReviewActivated fibroblasts are critically implicated in repair and remodeling of the injured heart. This manuscript discusses recent progress in the cell biology of fibroblasts in the infarcted and remodeling myocardium, highlighting advances in understanding the origin, function, and mechanisms of activation of these cells.Recent FindingsFollowing myocardial injury, fibroblasts undergo activation and myofibroblast transdifferentiation. Recently published studies have suggested that most activated myofibroblasts in the infarcted and pressure-overloaded hearts are derived from resident fibroblast populat...
Source: Current Pathobiology Reports - April 22, 2017 Category: Laboratory Medicine Source Type: research
Regulation of Exercise-Induced Autophagy in Skeletal Muscle
AbstractPurpose of ReviewPhysical exercise is a highly effective method to prevent several pathogenic conditions, such as obesity, type 2 diabetes, and cardiovascular diseases, largely due to metabolic adaptations induced by exercise in skeletal muscle. Yet how exercise induces the beneficial effects in muscle remains to be fully elucidated. Autophagy is a lysosomal degradation pathway that regulates nutrient recycling, energy production, and organelle quality control. The autophagy pathway is upregulated in response to stress during exercise and muscle contraction, and may be an important mechanism mediating exercise-indu...
Source: Current Pathobiology Reports - April 20, 2017 Category: Laboratory Medicine Source Type: research
Autophagy and Ferroptosis —What Is the Connection?
AbstractPurpose of ReviewAutophagy is a conserved intracellular degradation system and plays a dual role in cell death, depending on context and phase. Ferroptosis is a new form of regulated cell death that mainly depends on iron accumulation and lipid peroxidation. In this review, we summarize the processes of autophagy and ferroptosis and discuss their crosstalk mechanisms at the molecular level.Recent FindingsThe original study shows that ferroptosis is morphologically, biochemically, and genetically distinct from autophagy and other types of cell death. However, recent studies demonstrate that activation of ferroptosis...
Source: Current Pathobiology Reports - April 20, 2017 Category: Laboratory Medicine Source Type: research
Non-Canonical Activation of NRF2: New Insights and Its Relevance to Disease
AbstractPurpose of ReviewThe goal of this review is to summarize the current knowledge in the field regarding the non-canonical activation of the NRF2 pathway. Specifically, we address what role p62 plays in mediating this pathway, which pathologies have been linked to the p62-dependent activation of NRF2, as well as what therapeutic strategies could be used to treat diseases associated with the non-canonical pathway.Recent FindingsIt has recently been shown that autophagic dysfunction leads to the aggregation or autophagosomal accumulation of p62, which sequesters KEAP1, resulting in prolonged activation of NRF2. The abil...
Source: Current Pathobiology Reports - April 19, 2017 Category: Laboratory Medicine Source Type: research
The Influence of Extracellular RNA on Cell Behavior in Health, Disease, and Regeneration
AbstractPurpose of ReviewAn overview of the role of extracellular RNAs (exRNA) in the regulation of homeostasis, disease progression, and regeneration is provided herein. Several exRNAs have been identified as potential biomarkers for disease and disease progression. In addition, the potential of exRNAs as a therapeutic modality is discussed.Recent FindingsFibrotic diseases of the lung, liver, and heart, among other organs, share a number of identical exRNAs which play key roles in disease pathogenesis. Though regeneration is limited to only a few tissues in humans, small RNAs (e.g., microRNA) have been shown to be involve...
Source: Current Pathobiology Reports - January 31, 2017 Category: Laboratory Medicine Source Type: research
Discovery, Genomic Analysis, and Functional Role of the Erythrocyte RNAs
AbstractPurpose of ReviewHuman erythrocytes are responsible for oxygen delivery in the body. Erythrocytes are a product of terminal differentiated erythroid cells that accumulate hemoglobin and exclude nuclei. The long-held conventional wisdom has been that mature erythrocytes lack any genetic materials. Contrary to this view, accumulating evidence from multiple groups indicates that erythrocytes contain abundant and diverse RNA species. These newly discovered genetic materials suddenly open up opportunities to re-examine many diseases affecting erythrocytes.Recent FindingsThe genomic analysis and functional studies of the...
Source: Current Pathobiology Reports - January 31, 2017 Category: Laboratory Medicine Source Type: research
