Fatty acids bound to albumin are filtered through glomeruli, reabsorbed by proximal tubular epithelial cells, and metabolized. Because albumin serves as a carrier, an increase in delivery of fatty acids to the proximal tubule may occur in proteinuric states, possibly leading to toxic effects. At present, the contribution of fatty acids to tubulointerstitial damage and the mechanisms underlying this toxicity remain unclear. We recently found that the transcription factor peroxisome proliferator-activated receptor ␣ (PPAR␣) regulates fatty acid metabolism in proximal tubules, so we tested its role in tubular damage under proteinuric conditions. We induced protein-overload nephropathy in Ppara-null or wildtype (WT) mice by injecting fatty acids bound to BSA. Ppara-null mice exhibited greater renal dysfunction from severe proximal tubular injury than WT mice. Kidneys from Ppara-null mice injected with albumin alone showed little injury. Acute tubular injury was associated with deranged fatty acid homeostasis, increased oxidative stress, increased apoptosis, and activation of NFB signaling. These results suggest a role for fatty acids in proteinuria-associated tubular toxicity, as well as a protective role for PPAR␣. Modulation of PPAR␣ may be a future therapeutic option for tubular toxicity from fatty acids.
Mast cells are one of the constitutive cells in the interstitium of IgA nephritis patients and affect renal function by contributing to the interstitial fibrosis.
SUMMARY:Mast cells have become a recent concern in the nephrological world. The development of antibodies to mast cell-specific enzymes, tryptase and chymase, has facilitated the study of mast cells in the kidney. Now, they are investigated immunohistochemically as well as histochemically. There are three types of human mast cells, MC T , which contains exclusively tryptase, MC TC , which has both tryptase and chymase, and MC C , which contains only chymase. Many immunohistochemical studies involving mast cells have been conducted through the use of renal biopsy specimens. As a result, human renal diseases including various glomerulonephritis and pyelonephritis are found to have increased the number of mast cells in the renal cortex, especially in the area of fibrosis. The relationship between the number of mast cells and the prognosis of renal diseases has been proved to be significantly correlated in many reports. The subtypes of mast cells in these diseases are variably present, and no tendency of subtype specificity has been found. With the use of electron microscopically, mast cells are observed to be in contact with other interstitial cells or to infiltrate into tubules. Functionally, human renal mast cells resemble lung mast cells. Inhibitory substances for mast cell proliferation have been found in the mouse kidney. Compared with the results of human studies, mast cells are not found in the interstitum in animal models of renal diseases, except in a few transgenic mouse models and magnesium-deficient rats. Little is known about the exact roles that mast cells play in the renal interstitium. Future studies will hopefully make their characteristics clear.
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