In many cases, acute renal failure (ARF) is the result of proximal tubular cell injury and death and can arise in a variety of clinical situations, especially following renal ischemia and drug or toxicant exposure. Although much research has focused on the cellular events leading to ARF, less emphasis has been placed on the mechanisms of renal cell repair and regeneration, although ARF is rever...

The hypermuscular Compact phenotype was first noted in a line of mice selected for high body weight and protein content. A new line, based on mice showing the Compact phenotype, was formed and selected for maximum expression of the Compact phenotype. Previously we mapped and identified a 12-bp deletion in the myostatin gene, denoted Mstn, which can be considered as a major gene responsible for ...

Cardiac fibrosis is characterized by net accumulation of extracellular matrix in the myocardium and is an integral component of most cardiac pathological conditions. Fibrotic remodeling of the ventricle has profound consequences on cardiac function. Increased deposition of interstitial collagen in the perimysial space is initially associated with a stiffer ventricle and diastolic dysfunction. A...

ESTABLISHMENT OF AN ARTERIOVENOUS fistula (AVF) is an important step in providing hemodialysis in patients with chronic renal failure. However, over a period of months or years fistulous patency is compromised and that puts a tremendous constraint on hemodialysis therapy. Thus it is imperative to delineate the mechanisms that lead to the vascular access failure since such patients with dysfunct...

Pancreatic cancer is the fourth leading cause of cancer deaths in both men and women in the United States, accounting for 30,000 deaths annually. It is a deadly disease with a 5-year survival of only 3–5% (1). The diagnosis of pancreatic adenocarcinoma is devastating to patients and their families, because the diagnosis is usually made at a late stage of disease that is not amenable to cancer c...

Elastin is crucial to pulmonary function, yet it appears in the pulmonary vasculature and interstitium late in gestation in large mammals and postnatally in rodents (1). Deletion of the ELN gene in mice produces obstructive arterial disease (2, 3) and disrupts terminal airway branching as well as alveogenesis (4); moreover, several forms of elastic tissue disease collectively known as cutis lax...

The Notch signaling pathway comprises a family of transmembrane receptors, ligands, negative and positive modifiers, and transcription factors with regulatory activity in multiple cellular processes, including cell fate determination, development, differentiation, proliferation, apoptosis, and regeneration. A critical step in the activation of the Notch receptor is proteolytic cleavage of its i...

Glucose in chronic excess causes toxic effects on structure and function of organs, including the pancreatic islet. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. There ...

P atients with a chronic glomerulopathy are at risk for progressively declining renal function that results in end-stage renal failure irrespective of etiology. The underlying pathophysiology is at least partly dependent on maladaptive functional changes that occur in the surviving nephrons upon destruction of a critical number of glomeruli. In proteinuric nephropathies, the dysfunction of the ...

MEMBERS OF the fibroblast growth factor (FGF) family have been shown experimentally to stimulate angiogenesis through their mitotic and migratory effects on endothelial cells and by promoting endothelial integrity (2, 8). As such, they have been explored as a potential treatment of ischemic disease in several clinical trials (6). In their article in the issue of the American Journal of Physiolo...