5-Lypoxygenase Products Are Involved in Renal Tubulointerstitial Injury Induced by Albumin Overload in Proximal Tubules in Mice

Abstract

The role of albumin overload in proximal tubules (PT) in the development of tubulointerstitial injury and, consequently, in the progression of renal disease has become more relevant in recent years. Despite the importance of leukotrienes (LTs) in renal disease, little is known about their role in tubulointerstitial injury. The aim of the present work was to investigate the possible role of LTs on tubulointerstitial injury induced by albumin overload. An animal model of tubulointerstitial injury challenged by bovine serum albumin was developed in SV129 mice (wild-type) and 5-lipoxygenase-deficient mice (5-LO–/–). The changes in glomerular morphology and nestin expression observed in wild-type mice subjected to kidney insult were also observed in 5-LO–/– mice. The levels of urinary protein observed in the 5-LO–/– mice subjected or not to kidney insult were lower than those observed in respective wild-type mice. Furthermore, the increase in lactate dehydrogenase activity, a marker of tubule damage, observed in wild-type mice subjected to kidney insult did not occur in 5-LO–/– mice. LTB4 and LTD4, 5-LO products, decreased the uptake of albumin in LLC-PK1 cells, a well-characterized porcine PT cell line. This effect correlated with activation of protein kinase C and inhibition of protein kinase B. The level of proinflammatory cytokines, tumor necrosis factor-α and interleukin (IL)-6, increased in mice subjected to kidney insult but this effect was not modified in 5-LO–/– mice. However, 5-LO–/– mice subjected to kidney insult presented lower macrophage infiltration and higher levels of IL-10 than wild-type mice. Our results reveal that LTs have an important role in tubulointerstitial disease induced by albumin overload.

Effects of <i>Tripterygium wilfordii</i> Induction Therapy to IgA Nephropathy Patients with Heavy Proteinuria

“…Excessive amounts of proteinuria induced the expression of proinflammatory factors, including growth factors, cytokines, and chemokine, which lead to tubular damage. 28,29) In agreement with previous studies, 30) the majority of the study patients had significant degrees of tubulointerstitial injury, increased NAG and RBP.…”

Non-Transgenic Mouse Models of Kidney Disease

“…injections of bovine serum albumin (administered at a dose of 10 g/kg) causes proteinuria and tubulointerstitial fibrosis in mice from the 129 strain [39]. This effect is strain dependent and C57BL/6 mice are considered to be more resistant compared to the 129 strain and other mouse strains [4].…”

The Macrophage Phagocytic Receptor CD36 Promotes Fibrogenic Pathways on Removal of Apoptotic Cells during Chronic Kidney Injury

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