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。

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

Cell-matrix interactions have major effects upon phenotypic features such as gene regulation, cytoskeletal structure, differentiation, and aspects of cell growth control. Programmed cell death (apoptosis) is crucial for maintaining appropriate cell number and tissue organization. It was therefore of interest to determine whether cell-matrix interactions affect apoptosis. The present report demonstrates that apoptosis was induced by disruption of the interactions between normal epithelial cells and extracellular matrix. We have termed this phenomenon "anoikis." Overexpression of bcl-2 protected cells against anoikis. Cellular sensitivity to anoikis was apparently regulated: (a) anoikis did not occur in normal fibroblasts; (b) it was abrogated in epithelial cells by transformation with v-Ha-ras, v-src, or treatment with phorbol ester; (c) sensitivity to anoikis was conferred upon HT1080 cells or v-Ha-ras-transformed MDCK cells by reverse-transformation with adenovirus E1a; (d) anoikis in MDCK cells was alleviated by the motility factor, scatter factor. The results suggest that the circumvention of anoikis accompanies the acquisition of anchorage independence or cell motility.

/pdf/disruption-of-epithelial-cell-matrix-interactions-induces-4zrqjfm9bc.pdf

Disruption of epithelial cell-matrix interactions induces apoptosis

https://www.cell.com/developmental-cell/pdf/S1534-5807(08)00209-8.pdf

Epithelial-Mesenchymal Transition: At the Crossroads of Development and Tumor Metastasis

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.

/pdf/biomarkers-for-epithelial-mesenchymal-transitions-4rugbye0ja.pdf

Biomarkers for epithelial-mesenchymal transitions

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

/pdf/evidence-that-fibroblasts-derive-from-epithelium-during-4xrfjt8x5t.pdf

Evidence that fibroblasts derive from epithelium during tissue fibrosis

Ischemic acute renal failure: an inflammatory disease?

Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative impo...

https://www.annualreviews.org/doi/pdf/10.1146/annurev-med-050214-013407

Acute Kidney Injury.

https://www.ajkd.org/article/0272-6386(95)90610-X/pdf

Transformations Between Epithelium and Mesenchyme: Normal, Pathological, and Experimentally Induced

Acute renal failure (ARF) as a consequence of ischemic injury is a common disease affecting 5% of the hospitalized population. Despite the fact that mortality from ARF is high, there has been littl...

Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney

Epithelial cells polarize in response to contacts with the extracellular matrix and with neighboring cells. Interactions of cells with the extracellular matrix are mediated mainly by the integrin family of receptors. To begin to understand the role of integrins in polarization, we have investigated the expression and localization of three integrin families in the polarized Madin-Darby canine kidney (MDCK) epithelial cell line and in transformed MDCK cells lacking apical polarity. We find that MDCK cells express several beta 1 integrins, including alpha 2 beta 1, alpha 3 beta 1, and an unidentified integrin designated alpha x beta 1. The beta 1 integrins are the major receptors for collagens I and IV and laminin in MDCK cells, since a blocking anti-beta 1 antibody almost totally abolishes adhesion to these proteins. They also express a vitronectin receptor tentatively identified as alpha v beta 3, and the epithelial-specific integrin alpha 6 beta 4. The latter is not a laminin receptor in MDCK cells because a function blocking anti-alpha 6 antibody has no effect on cell adhesion to laminin. All three integrin families are expressed exclusively on both the basal and lateral surfaces, as determined by immunofluorescence microscopy and surface biotinylation. Transformed MDCK cells express beta 1 integrins as well as alpha v beta 3 and alpha 6 beta 4, but show alterations in the beta 1 family. Expression of alpha x is lacking, and the relative amount of the beta 1 subunit is diminished, resulting in the accumulation of Endo-H-sensitive alpha 3. In addition, surface biotinylation and immunofluorescence indicate that significant amounts of both alpha 2 beta 1 and alpha 3 beta 1 appear on not only the basolateral but also the apical plasma membrane. These results indicate that integrins are the major receptors for the extracellular matrix in MDCK cells, and that they may affect epithelial cell polarization by mediating not only cell-substratum but also cell-cell contacts.

Anna Zuk

Papers

Ischemic acute renal failure: an inflammatory disease?

Acute Kidney Injury.

Transformations Between Epithelium and Mesenchyme: Normal, Pathological, and Experimentally Induced

Polarity, integrin, and extracellular matrix dynamics in the postischemic rat kidney

Integrin expression and localization in normal MDCK cells and transformed MDCK cells lacking apical polarity.