Inflammation and caspase activation in long-term renal ischemia/reperfusion injury and immunosuppression in rats

Yang, Bin; Jain, Sunjay; Pawluczyk, Izabella Z. A.; Imtiaz, S; Bowley, Lucas; Ashra, Shairbanu Y.; Nicholson, Michael L.

doi:10.1111/j.1523-1755.2005.00662.x

Cited by 63 publications

(73 citation statements)

References 64 publications

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“…These findings might suggest that infiltrating macrophages play an important role in mediating renal injury. There are several other studies that investigate the relationship between the sustained inflammatory response and progressive renal injury following acute ischaemic/reperfusion injury [15][16][17][18]. They also demonstrated the renoprotective effect of immunosuppressive drug in reducing the inflammation [19].…”

Section: Discussionmentioning

confidence: 99%

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury

Ko¹,

Boo²,

Jo³

et al. 2007

Nephrology Dialysis Transplantation

183

109

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Background. Ischaemia/reperfusion is a major cause of acute kidney injury and can result in poor long-term graft function. Although most of the patients with acute kidney injury recover their renal function, significant portion of patients suffer from progressive deterioration of renal function. A persistent inflammatory response might be associated with long-term changes following acute ischaemia/reperfusion. Macrophages are known to infiltrate into tubulointersitium in animal models of chronic kidney disease. However, the role of macrophages in long-term changes after ischaemia/reperfusion remains unknown. We aimed to investigate the role of macrophages on the development of tubulointerstitial fibrosis and functional impairment following acute ischaemia/reperfusion injury by depleting macrophages with liposome clodronate. Methods. Male Sprague-Dawley rats underwent right nephrectomy and clamping of left renal vascular pedicle or sham operation. Liposome clodronate or phosphate buffered saline was administered for 8 weeks. Biochemical and histological renal damage and gene expression of various cytokines were assessed at 4 and 8 weeks after ischaemia/reperfusion. Results. Ischaemic/reperfusion injury resulted in persistent inflammation and tubulointerstital fibrosis with decreased creatinine clearance and increased urinary albumin excretion at 4 and 8 weeks. Macrophage depletion attenuated those changes. This beneficial effect was accompanied with a decrease in gene expression of inflammatory and profibrotic cytokines. Conclusions. These results suggest that macrophages play an important role in mediating persistent inflammation and fibrosis after ischaemia/reperfusion leading to a development of chronic kidney disease. Strategies targeting macrophage infiltration or activation can be useful in the prevention of development of chronic kidney disease following ischaemic injury.

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Section: Discussionmentioning

confidence: 99%

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury

Ko¹,

Boo²,

Jo³

et al. 2007

Nephrology Dialysis Transplantation

183

109

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“…In the diabetic Tg mice, urinary HEL level and gene expression of RAGE induced by oxidative stress were significantly lower than in the diabetic WT mice. Moreover, gene expressions of catalase [35,36] and Gpx1 [37,38], which are the principal antioxidant enzymes in the kidney, were significantly lower in the diabetic Tg than in the diabetic WT mice. At the same time, hL-FABP expression in the proximal tubules of diabetic Tg kidneys was upregulated.…”

mentioning

confidence: 99%

Amelioration of diabetic tubulointerstitial damage in liver-type fatty acid-binding protein transgenic mice

Kamijo‐Ikemori¹,

Sugaya²,

Sekizuka

et al. 2008

Nephrology Dialysis Transplantation

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Background. Renoprotection of liver-type fatty acid binding protein (L-FABP) was demonstrated in a streptozotocin (STZ)-induced diabetic mouse model. Methods. Established human L-FABP (hL-FABP)transgenic (Tg) mice and wild-type (WT) mice were divided into two groups: diabetic mice were uninephrectomized and injected with STZ; control mice were uninephrectomized and injected with a citrate buffer alone. Although mouse L-FABP was not expressed in WT mice, hL-FABP was expressed in the proximal tubules of the diabetic Tg mice and in the control Tg mice at 8 and 14 weeks after these injections. Results. The expression of renal hL-FABP increased significantly in diabetic Tg mice compared to control Tg mice. A number of macrophages (F4/80) infiltrating the interstitium, the gene expressions of MCP-1, MCP-3, TGF-β, Fas, Bax and RAGE were significantly lower in diabetic Tg kidneys compared with diabetic WT kidneys. In the diabetic Tg kidneys, the degree of the tubulointerstitial injury and the deposition of type IV collagen were significantly lower than that of diabetic WT kidneys. The expressions of catalase and glutathione peroxidase-1 were significantly lower in diabetic Tg kidneys compared with diabetic WT kidneys. Conclusions. Renal L-FABP ameliorated the tubulointerstitial damage of type 1 diabetic mice.

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“…Ischemia/reperfusion-induced renal injury (renal IRI) is the most common cause of acute renal failure (ARF), a major clinical problem with exceptionally high morbidity and mortality (9). The cause of renal IRI is complex, and it has been shown to be related to increased production of free radicals (and hence oxidative stress), inflammatory responses, and activation of apoptotic pathways (6,10,11). Oxidative stress contributes to cell damage in a variety of kidney diseases.…”

mentioning

confidence: 99%

Apoptosis Antagonizing Transcription Factor Protects Renal Tubule Cells against Oxidative Damage and Apoptosis Induced by Ischemia-Reperfusion

Xie¹,

Guo²

2006

Journal of the American Society of Nephrology

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Inflammation and caspase activation in long-term renal ischemia/reperfusion injury and immunosuppression in rats

Abstract: This study shows that the mechanisms of long-term I/R injury and immunosuppressants treatment include interstitial inflammation and caspase activation, most clearly demonstrated by the 24 kD active caspase-3.

Cited by 63 publications

References 64 publications

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury

Macrophages contribute to the development of renal fibrosis following ischaemia/reperfusion-induced acute kidney injury

Amelioration of diabetic tubulointerstitial damage in liver-type fatty acid-binding protein transgenic mice

Apoptosis Antagonizing Transcription Factor Protects Renal Tubule Cells against Oxidative Damage and Apoptosis Induced by Ischemia-Reperfusion

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