Eric G. Neilson

Bio: Eric G. Neilson is an academic researcher from Northwestern University. The author has contributed to research in topics: Antigen & Interstitial nephritis. The author has an hindex of 73, co-authored 247 publications receiving 29759 citations. Previous affiliations of Eric G. Neilson include University of Kansas & University of Michigan.

Epithelial-mesenchymal transition and its implications for fibrosis.

Abstract: Epithelial to mesenchymal transition (EMT) is a central mechanism for diversifying the cells found in complex tissues. This dynamic process helps organize the formation of the body plan, and while EMT is well studied in the context of embryonic development, it also plays a role in the genesis of fibroblasts during organ fibrosis in adult tissues. Emerging evidence from studies of renal fibrosis suggests that more than a third of all disease-related fibroblasts originate from tubular epithelia at the site of injury. This review highlights recent advances in the process of EMT signaling in health and disease and how it may be attenuated or reversed by selective cytokines and growth factors.

Stromal fibroblasts in cancer initiation and progression

Abstract: It is widely accepted that the development of carcinoma--the most common form of human cancer--is due to the accumulation of somatic mutations in epithelial cells. The behaviour of carcinomas is also influenced by the tumour microenvironment, which includes extracellular matrix, blood vasculature, inflammatory cells and fibroblasts. Recent studies reveal that fibroblasts have a more profound influence on the development and progression of carcinomas than was previously appreciated. These new findings have important therapeutic implications.

Biomarkers for epithelial-mesenchymal transitions

Abstract: In the early 19th century, building on observations of microscopists now ancient, Schleiden and Schwann formulated the doctrine that cells are building blocks for plant and animal tissues (1). By the mid-19th century, Raspail, Remak, and Virchow expanded this hypothesis by suggesting that all cells come from preexisting cells — the so-called cell theory. Although referring to cell division, this now classic notion is prescient of another contemporary twist in the biology of cell maturation: beyond lineage development and normal differentiation, mature epithelial cells under new environmental pressures exhibit a local plasticity that allows them to morph into other mature phenotypes with or without proliferation (2, 3). Growing interest in the biology of these cellular transitions helped both establish epithelial cell plasticity as a field of study in the late 20th century and fashion much of the current thinking regarding morphogenesis in early embryonic development, tissue repair, and cancer metastasis (4–6). The details of some of these processes are not discussed here, as they are outlined in other articles in this Review Series on epithelial-mesenchymal transition (EMT) (7, 8). Instead, we offer a personal view gathered from our own experience and the literature regarding an approach documenting EMT events in culture or tissue. We hope this serves to stimulate other points of view as new data emerge.

Evidence that fibroblasts derive from epithelium during tissue fibrosis

Abstract: Interstitial fibroblasts are principal effector cells of organ fibrosis in kidneys, lungs, and liver While some view fibroblasts in adult tissues as nothing more than primitive mesenchymal cells surviving embryologic development, they differ from mesenchymal cells in their unique expression of fibroblast-specific protein-1 (FSP1) This difference raises questions about their origin Using bone marrow chimeras and transgenic reporter mice, we show here that interstitial kidney fibroblasts derive from two sources A small number of FSP1(+), CD34(-) fibroblasts migrate to normal interstitial spaces from bone marrow More surprisingly, however, FSP1(+) fibroblasts also arise in large numbers by local epithelial-mesenchymal transition (EMT) during renal fibrogenesis Both populations of fibroblasts express collagen type I and expand by cell division during tissue fibrosis Our findings suggest that a substantial number of organ fibroblasts appear through a novel reversal in the direction of epithelial cell fate As a general mechanism, this change in fate highlights the potential plasticity of differentiated cells in adult tissues under pathologic conditions

Endothelial-to-mesenchymal transition contributes to cardiac fibrosis

Abstract: Cardiac fibrosis, associated with a decreased extent of microvasculature and with disruption of normal myocardial structures, results from excessive deposition of extracellular matrix, which is mediated by the recruitment of fibroblasts. The source of these fibroblasts is unclear and specific anti-fibrotic therapies are not currently available. Here we show that cardiac fibrosis is associated with the emergence of fibroblasts originating from endothelial cells, suggesting an endothelial-mesenchymal transition (EndMT) similar to events that occur during formation of the atrioventricular cushion in the embryonic heart. Transforming growth factor-β1 (TGF-β1) induced endothelial cells to undergo EndMT, whereas bone morphogenic protein 7 (BMP-7) preserved the endothelial phenotype. The systemic administration of recombinant human BMP-7 (rhBMP-7) significantly inhibited EndMT and the progression of cardiac fibrosis in mouse models of pressure overload and chronic allograft rejection. Our findings show that EndMT contributes to the progression of cardiac fibrosis and that rhBMP-7 can be used to inhibit EndMT and to intervene in the progression of chronic heart disease associated with fibrosis.

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Intensive Insulin Therapy in Critically Ill Patients

Abstract: Background Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. Methods We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter and maintenance of glucose at a level between 180 and 200 mg per deciliter). Results At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The ...

The basics of epithelial-mesenchymal transition

Abstract: The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.