Role of Calcium Oxalate Monohydrate Crystal Interactions with Renal Epithelial Cells in the Pathogenesis of Nephrolithiasis: A Review

Renal tubular fluid in the distal nephron is supersaturated with calcium and oxalate ions that nucleate to form crystals of calcium oxalate monohydrate (COM), the most common crystal in renal stones. How these nascent crystals are retained in the nephron to form calculi in certain individuals is not known. Recent studies from this laboratory have demonstrated that COM crystals can bind within seconds to the apical surface of renal epithelial cells, suggesting one mechanism whereby crystals could be retained in the tubule. Adherence of crystals to cells along the nephron may be opposed by specific urinary anions such as glycosaminoglycans, uropontin, nephrocalcin, and citrate. In culture, adherent crystals are quickly internalized by renal cells, and reorganization of the cytoskeleton, alterations in gene expression, and initiation of proliferation can ensue. Each of these cellular events appears to be regulated by extra-cellular factors. Identification of molecules in tubular fluid and on the cell surface that determine whether a crystal-cell interaction results in retention of the crystal or its passage out of the nephron appears critical for understanding the pathogenesis of nephrolithiasis

Adaptive Silviculture for Climate Change in the Mississippi National River and Recreation Area, an Urban National Park in the Twin Cities Area, Minnesota

The Adaptive Silviculture for Climate Change (ASCC) Network is a collaborative effort to establish a series of experimental silvicultural trials across different forest ecosystem types. A variety of partners have developed trial sites as part of this multi-regional study researching long-term ecosystem responses to a range of climate change adaptation actions. We are currently implementing an affiliate trial within the Mississippi National River and Recreation Area, a national park along the Mississippi River in the Twin Cities Metro Area of Minnesota

Calcium oxalate monohydrate crystals stimulate gene expression in renal epithelial cells

Calcium oxalate monohydrate crystals stimulate gene expression in renal epithelial cells. Primary or secondary hyperoxaluria is associated with calcium oxalate nephrolithiasis, interstitial fibrosis and progressive renal insufficiency. Monolayer cultures of nontransformed monkey kidney epithelial cells (BSC-1 line) and calcium oxalate monohydrate (COM) crystals were used as a model system to study cell responses to crystal interactions that might occur in the nephrons of patients during periods of hyperoxaluria. To determine if COM crystals signal a change in gene expression, Northern blots were prepared from total renal cellular RNA after the cells were exposed to crystals. The immediate early genes c-myc, EGR-1, and Nur-77 were induced at one hour. At two to six hours stimulated expression of the genes encoding plasminogen activator inhibitor (PAI-1) and platelet-derived growth factor (PDGF)-A chain was detected, but constitutive expression of urokinase-type plasminogen activator (u-PA) was not altered. Expression of connective tissue growth factor (CTGF) was induced at one hour and persisted up to 24 hours. The stimulation of gene expression by COM crystals was relatively crystal- and renal cell-type specific. Thus the interaction of kidney epithelial cells with COM crystals alters expression of genes that encode three classes of proteins: transcriptional activators, a regulator of extracellular matrix (ECM), and growth factors. Activation of PAI-1 gene expression without a change in u-PA favors accumulation of ECM proteins, as does increased expression of PDGF and CTGF which can also stimulate fibroblast proliferation in a paracrine manner. These results suggest that COM crystal-mediated stimulation of specific genes in renal tubular cells may contribute to the development of interstitial fibrosis in hyperoxaluric states

Distinct and conserved transcriptomic changes during nematode-induced giant cell development in tomato compared with Arabidopsis: a functional role for gene repression

Summary: Root-knot nematodes (RKNs) induce giant cells (GCs) from root vascular cells inside the galls. Accompanying molecular changes as a function of infection time and across different species, and their functional impact, are still poorly understood. Thus, the transcriptomes of tomato galls and laser capture microdissected (LCM) GCs over the course of parasitism were compared with those of Arabidopsis, and functional analysis of a repressed gene was performed. Microarray hybridization with RNA from galls and LCM GCs, infection–reproduction tests and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) transcriptional profiles in susceptible and resistant (Mi-1) lines were performed in tomato. Tomato GC-induced genes include some possibly contributing to the epigenetic control of GC identity. GC-repressed genes are conserved between tomato and Arabidopsis, notably those involved in lignin deposition. However, genes related to the regulation of gene expression diverge, suggesting that diverse transcriptional regulators mediate common responses leading to GC formation in different plant species. TPX1, a cell wall peroxidase specifically involved in lignification, was strongly repressed in GCs/galls, but induced in a nearly isogenic Mi-1 resistant line on nematode infection. TPX1 overexpression in susceptible plants hindered nematode reproduction and GC expansion. Time-course and cross-species comparisons of gall and GC transcriptomes provide novel insights pointing to the relevance of gene repression during RKN establishment