Effects of Metalloproteinase Inhibition in a Murine Model of Renal Ischemia-Reperfusion Injury

Novak, Katherine B.; Le, Hau D.; Christison‐Lagay, Emily R.; Nosé, Vânia; Doiron, Robert; Moses, Marsha A.; Puder, Mark

doi:10.1203/pdr.0b013e3181ca0aa2

Cited by 37 publications

(34 citation statements)

References 45 publications

(48 reference statements)

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“…Urinary MMP-9, in combination with other markers, could serve as a biomarker of AKI (40). A wide variety of AKI models have characterized an increase in the expression of MMP-2 and MMP-9 as well as MMP-7 (8,11,91). Although methods to decrease MMP activity generally reduce injury in the majority of experimental models, at least one study shows that MMP-9 knockouts did worse, due to a diminished antiapoptotic signaling through stem cell factor (Table 2).…”

Section: Mmps In Renal Pathologymentioning

confidence: 99%

Matrix metalloproteinases in kidney homeostasis and diseases

Tan

Liu

2012

American Journal of Physiology-Renal Physiology

216

219

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Section: Mmps In Renal Pathologymentioning

confidence: 99%

Matrix metalloproteinases in kidney homeostasis and diseases

Tan

Liu

2012

American Journal of Physiology-Renal Physiology

216

219

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“…Renal injury following IRI does not improve and typically worsens over time. As an organ with high perfusion rates, the kidneys are sensitive to reperfusion following ischemia (2). Therefore, renal IRI is likely to occur following kidney transplant, kidney vascular surgery, extracorporeal shock wave lithotripsy or resuscitation (3).…”

Section: Introductionmentioning

confidence: 99%

Pterostilbene protects against acute renal ischemia reperfusion injury and inhibits oxidative stress, inducible nitric oxide synthase expression and inflammation in rats via the Toll‑like receptor 4/nuclear factor‑κB signaling pathway

et al. 2017

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Abstract. Previous studies have demonstrated that pterostilbene (Pter) prevents oxidative stress, suppresses cell growth and exhibits anti-fungal and anti-inflammatory effects. Pter is used to treat a number of clinical diseases, including Alzheimer's disease, various malignancies and hypercholesteremia. The aim of the present study was to investigate whether Pter protects against acute renal ischemia reperfusion injury (IRI) and inhibits oxidative stress, inducible nitric oxide synthase (iNOS) expression and inflammation in rats. A total of 40 adult male Sprague Dawley rats were divided into the following 5 groups at random: Control group, where rats were not subjected to renal IRI; IRI group, where rats were subjected to renal IRI; Pter 10 group, where rats underwent renal IRI and were treated with 10 mg/kg Pter; Pter 20 group, where rats underwent renal IRI and were treated with 20 mg/kg Pter; Pter 30 group, where rats underwent renal IRI and were treated with 30 mg/kg Pter. The results demonstrated that Pter treatment improved renal function following acute renal IRI. Compared with the untreated renal IRI group, myeloperoxidase, iNOS, interleukin (IL)-1β, IL-6 and tumor necrosis factor-α expression levels were significantly decreased (P<0.01), whereas IL-10 expression levels were significantly increased (P<0.01) following treatment with Pter in acute renal IRI rats. In addition, Pter significantly attenuated caspase-3 activity and the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signaling pathway induced by acute renal IRI (P<0.01). These results provide evidence to suggest that administration of Pter may protect against acute renal IRI and inhibit oxidative stress, iNOS expression and inflammation in rats via the TLR4/NF-κB signaling pathway.

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“…In our previous study, we demonstrated that ischemic AKI induces up-regulation of matrix metalloproteinases (MMPs), which results in a proteolytic degradation of -renal microvascular matrix, with potential destruction of peritubular capillaries and subsequent worsening of acute tubular injury (ATI) [14]. Furthermore, inhibition of MMPs protected against such damage and suppressed subsequent progression of AKI, findings that have created interest in MMP inhibitors as drugs for AKI [14,15]. Recent studies, however, highlighted the beneficial roles of MMPs in tissue remodeling and/or recovery in several diseases and organ injuries, including ischemia/reperfusion injury [16,17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

Role of Matrix Metalloproteinase-2 in Recovery after Tubular Damage in Acute Kidney Injury in Mice

Kaneko

Shimizu²,

Mii

et al. 2013

Nephron Exp Nephrol

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Background/Aims: Matrix metalloproteinases (MMPs) are zinc endopeptidases that degrade extracellular matrix and are involved in the pathogenesis of ischemic damage in acute kidney injury (AKI). In the present study, we analyzed the role of MMP-2 in the repair process in ischemic AKI. Methods: AKI was induced in MMP-2 wild-type (MMP-2^+/+) and MMP-2-deficient (MMP-2^-/-) mice by 90-min renal artery clamping followed by reperfusion. Renal histology and the activity and distribution of MMP-2 were examined from day 1 to day 14. During the recovery from AKI, MMP-2^+/+ mice were also treated with MMP-2/MMP-9 inhibitor. Results: In both MMP-2^+/+ and MMP-2^-/- mice, AKI developed on day 1 after ischemia/reperfusion with widespread acute tubular injury, but subsequent epithelial cell proliferation was evident on days 3-7. During the repair process, active MMP-2 and MMP-9 increased in regenerating tubular epithelial cells in MMP-2^+/+ mice on days 7-14, and the tubular repair process was almost complete by day 14. On the other hand, in MMP-2^-/- mice, less prominent proliferation of tubular epithelial cells was evident on days 3 and 7, and damaged tubules that were covered with elongated and immature regenerated epithelial cells were identified on days 7 and 14. Incomplete recovery of injured microvasculature was also noted with persistent macrophage infiltration. Similarly, treatment with MMP-2/MMP-9 inhibitor resulted in impaired recovery in MMP-2^+/+ mice. Conclusion: MMP-2 is involved in tubular repair after AKI. The use of the MMP-2/MMP-9 inhibitor was a disadvantage when it was administered during the repair stage of ischemic AKI. Treatment with MMP inhibitor for AKI needs to be modified to enhance recovery from AKI.

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Effects of Metalloproteinase Inhibition in a Murine Model of Renal Ischemia-Reperfusion Injury

Cited by 37 publications

References 45 publications

Matrix metalloproteinases in kidney homeostasis and diseases

Matrix metalloproteinases in kidney homeostasis and diseases

Pterostilbene protects against acute renal ischemia reperfusion injury and inhibits oxidative stress, inducible nitric oxide synthase expression and inflammation in rats via the Toll‑like receptor 4/nuclear factor‑κB signaling pathway

Role of Matrix Metalloproteinase-2 in Recovery after Tubular Damage in Acute Kidney Injury in Mice

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