Genetic deficiency of adiponectin protects against acute kidney injury

Jin, Xiaogao; Chen, Jiyuan; Hu, Zhaoyong; Chan, Lawrence; Wang, Yanlin

doi:10.1038/ki.2012.408

Cited by 71 publications

(88 citation statements)

References 50 publications

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“…The above-mentioned studies should be considered separately from studies investigating the role of adiponectin in the setting of acute renal injury. The latter group of studies includes two trials investigating whether adiponectin can modulate the adverse effects of renal ischemia-reperfusion injury in mice (Cheng et al 2012, Jin et al 2013. These studies yielded conflicting results with regard to the acute responses of various parameters of renal structure and function resulting from acute renal injury.…”

Section: The Role Of Adiponectin In Renal Physiologymentioning

confidence: 99%

The role of adiponectin in renal physiology and development of albuminuria

Christou¹,

Kiortsis²

2014

Journal of Endocrinology

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Adiponectin is secreted by the adipose tissue and is downregulated in states of obesity and insulin resistance. There is a growing body of evidence indicating that adiponectin has renoprotective effects and protects against the development of albuminuria in rodent experiments. Adiponectin crossing the glomerular filtration barrier possibly inhibits inflammation, fibrosis and oxidative stress in kidneys through activation of AMP-activated protein kinase. Moreover, microalbuminuria is a well established early sign of progressive cardiovascular and renal disease, even in subjects with preserved glomerular filtration rate. Studies investigating the relationship between serum adiponectin levels and urinary albumin excretion rate (UAE) have yielded conflicting data and the mechanisms underlying the interplay between adiponectin and albuminuria remain to be elucidated. This article constitutes a critical review attempting to clarify any remaining confusion about this matter. Furthermore, this article examines the clinical significance of adiponectin-albuminuria interplay, suggesting that adiponectin is possibly involved in the development of albuminuria that is associated with obesity, diabetes and cardiovascular disease and may mediate, at least in part, the actions of medical treatments that influence UAE, such as angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, thiazolidinediones, fenofibrate and diet. Further studies to investigate more thoroughly the renoprotective role of adiponectin in the human setting should be carefully planned, focusing on causality and the possible influence of adiponectin on the development of albuminuria in specific clinical settings.

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Section: The Role Of Adiponectin In Renal Physiologymentioning

confidence: 99%

The role of adiponectin in renal physiology and development of albuminuria

Christou¹,

Kiortsis²

2014

Journal of Endocrinology

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“…6,7,17,42,43 Bone Marrow Transplantation Bone marrow transplantation was performed as previously described. 6,10,17,42,44 Briefly, bone marrow cells (5310 6 ) from WT or STAT6 KO mice were transferred to lethally irradiated WT mice. Chimeric mice were allowed to recuperate for 7-8 weeks before UUO surgery.…”

Section: Animals and Uuo Surgerymentioning

confidence: 99%

JAK3/STAT6 Stimulates Bone Marrow–Derived Fibroblast Activation in Renal Fibrosis

Yan

Zhang

Yang

et al. 2015

Journal of the American Society of Nephrology

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125

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Renal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. Bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow-derived fibroblast precursors in the kidney are not fully understood. In this study, we investigated the role of the Janus kinase 3 (JAK3)/ signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrowderived fibroblasts. In cultured mouse monocytes, IL-4 or IL-13 activated STAT6 and induced expression of a-smooth muscle actin and extracellular matrix proteins (fibronectin and collagen I), which was abolished by a JAK3 inhibitor (CP690,550) in a dose-dependent manner or blocked in the absence of STAT6. In vivo, STAT6 was activated in interstitial cells of the obstructed kidney, an effect that was abolished by CP690,550. Mice treated with CP690,550 accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys compared with vehicle-treated mice. Treatment with CP690,550 also significantly reduced myofibroblast transformation, matrix protein expression, fibrosis development, and apoptosis in obstructed kidneys. Furthermore, STAT6-deficient mice accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys, produced less extracellular matrix protein, and developed much less fibrosis. Finally, wild-type mice engrafted with STAT6 2/2 bone marrow cells displayed fewer bone marrow-derived fibroblasts in the obstructed kidneys and showed less severe renal fibrosis compared with wild-type mice engrafted with STAT6 +/+ bone marrow cells. Our results demonstrate that JAK3/STAT6 has an important role in bone marrow-derived fibroblast activation, extracellular matrix production, and interstitial fibrosis development.

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“…4) It has also been observed that the p53-Bax-caspase-3 apoptotic pathway is involved in renal I/R injury. 4,5) P53 can induce the downregulation of anti-apoptotic Bcl-2 and the upregulation of pro-apoptotic Bax. A decrease in the Bcl-2/Bax ratio triggers cytochrome c release from mitochondria, which results in the activation of caspase-3 and a chain reaction leading to apoptosis.…”

mentioning

confidence: 99%

Isoflurane Preconditioning Ameliorates Renal Ischemia-Reperfusion Injury through Antiinflammatory and Antiapoptotic Actions in Rats

Liang

et al. 2014

Biological & Pharmaceutical Bulletin

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Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury via inflammation and cell apoptosis. Volatile anesthetics have been shown to exert organ-protective effects against kidney damage in vivo and in vitro. In the present study, we investigated the effects of isoflurane, a commonly used volatile anesthetic, on renal I/R injury and the underlying mechanisms. Rats subjected to renal I/R displayed higher serum creatinine and blood urea nitrogen levels than sham rats as well as severe histopathological damage. Renal I/R also resulted in a nuclear factor-κB (NF-κB)-mediated inflammatory response and dysfunction of the p53-Bax-caspase-3 apoptotic pathway. Rats preconditioned with 1.5% isoflurane for 2 h had better renal function and less tubular apoptosis 24 h after I/R injury than control rats. Pretreatment with isoflurane suppressed renal NF-κB activation, leading to a reduction in proinflammatory molecules (high-mobility group box 1, interleukin-1β, and tumor necrosis factor-α) both in the kidneys and circulation. In addition, rats subjected to isoflurane preconditioning had a higher Bcl-2/Bax ratio and less cleaved caspase-3. Our findings suggest that preconditioning with a clinically relevant concentration of isoflurane attenuates renal I/R injury, based at least in part on its ability to modulate renal inflammation and apoptosis.Key words acute kidney injury; ischemia-reperfusion; volatile anesthetic; inflammation; apoptosis Renal ischemic-reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), which occurs in many clinical settings including shock, renal transplantation, and renal artery angioplasty.1) Renal I/R injury always implies a poor prognosis and no effective therapy is currently available. Although the underlying mechanisms for renal I/R injury have been extensively studied, the pathophysiologic process involving inflammation and cell apoptosis and its relationship to subsequent renal injury remain to be fully elucidated.Nuclear factor-κB (NF-κB) is one of the most critical transcription factors involved in many inflammatory conditions, including renal I/R injury. Activation of NF-κB is a critical step in the systemic and renal inflammatory response, which leads to the release of proinflammatory cytokines including high-mobility group box 1 (HMGB1), 2) interleukin-1β (IL-1β), 3) and tumor necrosis factor-α (TNF-α).4) It has also been observed that the p53-Bax-caspase-3 apoptotic pathway is involved in renal I/R injury. 4,5) P53 can induce the downregulation of anti-apoptotic Bcl-2 and the upregulation of pro-apoptotic Bax. A decrease in the Bcl-2/Bax ratio triggers cytochrome c release from mitochondria, which results in the activation of caspase-3 and a chain reaction leading to apoptosis.6,7) Therefore, inhibiting the coexisting processes of inflammation and apoptosis provides a potential approach to the prevention and treatment of renal I/R injury.Isoflurane is a volatile anesthetic commonly used in clinical surgical settings. Previous studies have indicated ...

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Genetic deficiency of adiponectin protects against acute kidney injury

Cited by 71 publications

References 50 publications

The role of adiponectin in renal physiology and development of albuminuria

The role of adiponectin in renal physiology and development of albuminuria

JAK3/STAT6 Stimulates Bone Marrow–Derived Fibroblast Activation in Renal Fibrosis

Isoflurane Preconditioning Ameliorates Renal Ischemia-Reperfusion Injury through Antiinflammatory and Antiapoptotic Actions in Rats

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