Phenotypic Changes in Hepatic Stellate Cells in Response to Toxic Liver Injury
Abstract
Hepatic stellate cells (HSCs) are the main extracellular matrix-producing cell type in the liver. These cells exist in a quiescent state in normal liver and an activated state in damaged liver. During quiescence, HSCs store and release various retinoids. After injury to the liver, however, various protein and non-protein mediators are released from cells that stimulate HSCs to differentiate into myofibroblasts, a process termed activation. Activated HSCs begin to express α-smooth muscle actin and migrate to sites of injury through chemotaxis. Within the damaged region of liver, these cells becom...
Source: Current Pathobiology Reports - September 17, 2014 Category: Laboratory Medicine Source Type: research
New Approaches for Studying Alcoholic Liver Disease
Abstract
Alcoholic liver disease (ALD) is major cause of chronic liver injury which results in liver fibrosis and cirrhosis. According to the surveillance report published by the National Institute on Alcohol Abuse and Alcoholism, liver cirrhosis is the 12th leading cause of death in the United States with 48 % of these deaths being attributed to excessive alcohol consumption. ALD includes a spectrum of disorders from simple steatosis to steatohepatitis, fibrosis, and hepatocellular carcinoma. Several mechanisms play a critical role in the pathogenesis of ALD. These include ethanol–induced oxidative st...
Source: Current Pathobiology Reports - September 14, 2014 Category: Laboratory Medicine Source Type: research
Portal Fibroblasts in Biliary Fibrosis
Abstract
Portal fibroblasts are a minor population in the normal liver, found in the periportal mesenchyme surrounding the bile ducts. While many researchers have hypothesized that they are an important myofibroblast precursor population in biliary fibrosis, responsible for matrix deposition in early fibrosis and for recruiting hepatic stellate cells, the role of portal fibroblasts relative to hepatic stellate cells is controversial. Several papers published in the past year have addressed this point and have identified other potential roles for portal fibroblasts in biliary fibrosis. The goal of this rev...
Source: Current Pathobiology Reports - September 14, 2014 Category: Laboratory Medicine Source Type: research
Strategies to Detect Hepatic Myofibroblasts in Liver Cirrhosis of Different Etiologies
Abstract
Liver cirrhosis, a late stage of hepatic fibrosis, is an increasing cause of morbidity and mortality worldwide. Hepatic fibrosis is mainly caused by alcoholic or non-alcoholic steatohepatitis, chronic viral hepatitis, or autoimmune and biliary diseases. Myofibroblasts, which are absent from the normal liver, are differentiated from heterogeneous cell populations in response to a liver injury of any etiology and produce the extracellular matrix. Hepatic stellate cells are considered the main source of myofibroblasts. However, the origin of hepatic myofibroblasts remains unresolved, and despite con...
Source: Current Pathobiology Reports - September 14, 2014 Category: Laboratory Medicine Source Type: research
MicroRNAs in TGF-β/Smad-mediated Tissue Fibrosis
Abstract
Fibrosis is a key process leading to the end-stage organ scarring with loss of functions in a number of human diseases, contributes to about 45 % of deaths in the industrialized world. TGF-β signaling is one of the most important pathways for fibrogenesis in the diseased tissues. Increasing evidence shows that Smad3 is an important mediator of TGF-β/Smad signaling which enhances fibrosis by directly regulating the microRNAs (miRNAs) at transcriptional level. Recent studies clearly show an important role of miRNAs in the pathogenesis of tissue fibrosis in response to TGF-β. It has been reporte...
Source: Current Pathobiology Reports - September 14, 2014 Category: Laboratory Medicine Source Type: research
The Role of Dendritic Cells in Renal Inflammation
Abstract
Dendritic cells are central orchestrators of the immune response. They communicate with both innate and adaptive immune systems and can aggravate or attenuate renal inflammation depending on the microenvironment and the stage of disease. This review summarizes current knowledge regarding the role of dendritic cells in renal inflammation and highlights the recent advances in understanding their function in the development and resolution of various experimental and human kidney diseases. We anticipate that recent advances in this research area will yield in the near future novel therapeutic strateg...
Source: Current Pathobiology Reports - September 13, 2014 Category: Laboratory Medicine Source Type: research
Mitochondrial MicroRNAs and Their Potential Role in Cell Function
Abstract
Mitochondria are cellular powerhouses and central organelles to the regulation of many biological processes, including cell death and metabolism, with mitochondrial dysfunction being a hallmark of many different diseases. MicroRNAs (miRNAs) are a growing class of endogenous non-coding RNAs, which function as master regulators and fine-tuners of the genome, primarily via post-transcriptional mechanisms. miRNAs and RNA interference components have recently been demonstrated to be present in mitochondria from several species. However, miRNA transport mechanisms, biological targets, and function at...
Source: Current Pathobiology Reports - September 1, 2014 Category: Laboratory Medicine Source Type: research
MicroRNAs in Cholangiopathies
Abstract
Cholangiocytes, the cells lining bile ducts, comprise a small fraction of the total cellular component of the liver, yet perform the essential role of bile modification and transport of biliary and blood constituents. Cholangiopathies are a diverse group of biliary disorders with the cholangiocyte as the target cell; the etiopathogenesis of most cholangiopathies remains obscure. MicroRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression. These small RNAs may not only be involved in the etiopathogenesis of disease, but are also showing promise as diagnostic and prog...
Source: Current Pathobiology Reports - September 1, 2014 Category: Laboratory Medicine Source Type: research
Recent Advances in Understanding of NASH: MicroRNAs as Both Biochemical Markers and Players
Abstract
Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are becoming the dominant liver diseases in the US and Western World. Extensive work is being done to diagnose, understand, and explore the pathogenesis of these multivariable complex diseases. Recently, a new avenue of biologic regulation is being explored. MicroRNAs are noncoding RNAs that modulate the expression of multiple genes and have been implicated in multiple diseases. Recently, there is a growing body of evidence supporting a significant role of microRNAs in NAFLD pathogenesis and progression to NASH, an...
Source: Current Pathobiology Reports - September 1, 2014 Category: Laboratory Medicine Source Type: research
miRNA Expression in Mesenchymal Stem Cells
Abstract
Mesenchymal stem cells (MSCs) express defined patterns of miRNAs which have been shown to be involved in stemness and differentiation processes. Modulation of miRNA expression by MSCs has been shown to change their biological properties. Moreover, in light of the paracrine hypothesis of MSC action, increasing evidence indicates that miRNA transfer between MSCs and injured cells in tissues accounts for the healing properties exhibited by MSCs. Extracellular vesicles (EVs) are candidates for the trafficking of encapsulated miRNAs between cells, as they are able to cross easily biological barriers...
Source: Current Pathobiology Reports - September 1, 2014 Category: Laboratory Medicine Source Type: research
MicroRNAs in ER Stress: Divergent Roles in Cell Fate Decisions
Abstract
MicroRNAs are small, noncoding RNAs which regulate protein expression post-transcriptionally. They respond to changes in a cell's environment and can promote cell death or cell survival depending on the context. Recent studies have linked microRNAs to the unfolded protein response pathway. This pathway is activated in the endoplasmic reticulum by conditions which interfere with the normal functions of the endoplasmic reticulum. The cell fate outcomes consequent to the activation of the unfolded protein response are binary, either cell survival or cell death. MicroRNAs can regulate multiple comp...
Source: Current Pathobiology Reports - September 1, 2014 Category: Laboratory Medicine Source Type: research
Zebrafish Models of Biliary Atresia and Other Infantile Cholestatic Diseases
Abstract
Zebrafish are a powerful tool for the study of diseases that appear during development. Over the past decade, several zebrafish models of diseases that affect the developing liver in infants have been generated, including models of the most common identifiable cause of neonatal cholestasis, biliary atresia (BA). While none of these models exactly duplicate the disorder, studies on the zebrafish models have uncovered potentially important features of BA such as an importance of epigenetic changes and an association with specific mutations. In addition, other models replicate other cholestatic di...
Source: Current Pathobiology Reports - June 1, 2014 Category: Laboratory Medicine Source Type: research
Danio rerio: Small Fish Making a Big Splash in Leukemia
Abstract
Zebrafish (Danio rerio) are widely used for developmental biology studies. In the past decade, D. rerio have become an important oncology model as well. Leukemia is one type of cancer where zebrafish are particularly valuable. As vertebrates, fish have great anatomic and biologic similarity to humans, including their hematopoietic and immune systems. As an experimental platform, D. rerio offer many advantages that mammalian models lack. These include their ease of genetic manipulation, capacity for imaging, and suitability for large-scale phenotypic and drug screens. In this review, we p...
Source: Current Pathobiology Reports - June 1, 2014 Category: Laboratory Medicine Source Type: research
Zebrafish as a Model for Studying Cardiac Regeneration
Abstract
Heart failure caused by cardiomyocyte loss after ischemic tissue damage is a leading cause of death worldwide. Although adult mammalian cardiomyocytes are able to proliferate during normal aging and after infarction, they do so at insufficient rates for effective cardiac regeneration. Likewise, none of several described cardiac stem cell populations appear to form significant numbers of cardiomyocytes in ischemic hearts. Thus, adult mammals cannot regenerate heart injuries. Zebrafish, on the contrary, are able to regenerate multiple organs including amputated fins, lesioned brain, retina, spina...
Source: Current Pathobiology Reports - June 1, 2014 Category: Laboratory Medicine Source Type: research
Zebrafish as a Model for Studying Kidney Regeneration
Abstract
Kidney disease affects millions of people and represents a growing health care burden. There is no cure for loss of kidney function, because humans are born with a finite number of nephrons with limited ability to repair themselves after injury. Zebrafish kidneys have the remarkable ability to regenerate after injury by adding new nephrons as well as repairing existing nephrons as mammals do. In fish, new nephrons are able to differentiate in situ and functionally connect to the existing tubular architecture throughout the life of the adult animal. Zebrafish kidney regeneration allows investiga...
Source: Current Pathobiology Reports - June 1, 2014 Category: Laboratory Medicine Source Type: research
