scholarly journals Kidney injury molecule‐1 (KIM‐1)‐mediated anti‐inflammatory activity is preserved by Mucin 1 (MUC1) induction in the proximal tubule during ischemia‐reperfusion injury

2021 ◽  
Vol 35 (S1) ◽  
Author(s):  
Mohammad Al‐bataineh ◽  
Carol Kinlough ◽  
Zaichuan Mi ◽  
Edwin Jackson ◽  
David Emlet ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Inflammatory Activity ◽  
Mucin 1 ◽  
Anti Inflammatory ◽  
Kidney Injury Molecule 1

scholarly journals KIM-1-mediated anti-inflammatory activity is preserved by MUC1 induction in the proximal tubule during ischemia-reperfusion injury.

2021 ◽  
Author(s):  
Mohammad M Al-bataineh ◽  
Carol L Kinlough ◽  
Zaichuan Mi ◽  
Edwin K Jackson ◽  
Stephanie Mutchler ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mdck Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Inflammatory Activity ◽  
Mucin 1 ◽  
Anti Inflammatory ◽  
Kidney Injury Molecule 1

Cell-associated kidney injury molecule-1 (KIM-1) exerts an anti-inflammatory role following kidney injury by mediating efferocytosis and down regulating the NF-kB pathway. KIM-1 cleavage blunts its anti inflammatory activities. We reported that Mucin 1 (MUC1) is protective in a mouse model of ischemia reperfusion injury (IRI). As both KIM-1 and MUC1 are induced in the proximal tubule (PT) during IRI and are ADAM17 substrates, we tested the hypothesis that MUC1 protects KIM-1 activity. Muc1 KO mice and wild type (WT) littermates were subjected to IRI. KIM-1, MUC1 and ADAM17 levels (and signaling pathways) were assessed by immunoblotting. PT localization was assessed by confocal microscopy and in situ35proximity ligation assay. Findings were extended using human kidneys and urine, and KIM-1-mediated efferocytosis assays in mouse PT cultures.In response to tubular injury in mouse and human kidneys, we observed induction and co-expression of KIM-1 and MUC1 in the PT. Compared to WT, Muc1 KO mice had higher urinary KIM-1 and lower kidney KIM-1. KIM-1 was apical in PT of WT kidneys, but predominately with luminal debris in Muc1 KO mice. Efferocytosis was reduced in Muc1 KO PT cultures when compared to WT cells, while inflammation was increased in Muc1 KO kidneys when compared to WT mice. MUC1 was cleaved by ADAM17 in PT cultures, and blocked KIM-1 shedding in MDCK cells. We conclude that KIM-1-mediated efferocytosis and thus anti-inflammatory activity during IRI is preserved in the injured kidney by MUC1 inhibition of KIM-1 shedding.

scholarly journals KIM-1-mediated anti-inflammatory activity is preserved by MUC1 induction in the proximal tubule during ischemia-reperfusion injury

2021 ◽  
Author(s):  
Mohammad M Al-bataineh ◽  
Carol L Kinlough ◽  
Zaichuan Mi ◽  
Edwin Kerry Jackson ◽  
Stephanie Mutchler ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mdck Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Inflammatory Activity ◽  
Proximity Ligation Assay ◽  
Mucin 1 ◽  
Anti Inflammatory

Cell-associated kidney injury molecule-1 (KIM-1) exerts an anti-inflammatory role following kidney injury by mediating efferocytosis and downregulating the NF-kB pathway. KIM-1 cleavage blunts its anti-inflammatory activities. We reported that Mucin 1 (MUC1) is protective in a mouse model of ischemia-reperfusion injury (IRI). As both KIM-1 and MUC1 are induced in the proximal tubule (PT) during IRI and are ADAM17 substrates, we tested the hypothesis that MUC1 protects KIM-1 activity. Muc1 KO mice and wild-type (WT) littermates were subjected to IRI. KIM-1, MUC1 and ADAM17 levels (and signaling pathways) were assessed by immunoblotting. PT localization was assessed by confocal microscopy and in situ proximity ligation assay. Findings were extended using human kidneys and urine, and KIM-1-mediated efferocytosis assays in mouse PT cultures. In response to tubular injury in mouse and human kidneys, we observed induction and co-expression of KIM-1 and MUC1 in the PT. Compared to WT, Muc1 KO mice had higher urinary KIM-1 and lower kidney KIM-1. KIM-1 was apical in PT of WT kidneys, but predominately with luminal debris in Muc1 KO mice. Efferocytosis was reduced in Muc1 KO PT cultures when compared to WT cells, while inflammation was increased in Muc1 KO kidneys when compared to WT mice. MUC1 was cleaved by ADAM17 in PT cultures, and blocked KIM-1 shedding in MDCK cells. We conclude that KIM-1-mediated efferocytosis and thus anti-inflammatory activity during IRI is preserved in the injured kidney by MUC1 inhibition of KIM-1 shedding.

Endogenous PPARγ mediates anti-inflammatory activity in murine ischemia-reperfusion injury

2001 ◽  
Vol 120 (2) ◽  
pp. 460-469 ◽  
Author(s):  
Atsushi Nakajima ◽  
Koichiro Wada ◽  
Hiroshi Miki ◽  
Naoto Kubota ◽  
Noriko Nakajima ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Activity ◽  
Anti Inflammatory

Abstract 193: Antithrombin Perfluorocarbon Nanoparticles Ameliorate Renal Injury Following Transient Warm Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Chandu Vemuri ◽  
Junjie Chen ◽  
Rohun U Palekar ◽  
John S Allen ◽  
Xiaoxia Yang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Renal Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Warm Ischemia ◽  
P Value ◽  
Sprague Dawley ◽  
Histologic Analysis ◽  
Microvascular Thrombosis

Objective: Thrombin mediated microvascular thrombosis plays a crucial role in the pathogenesis of acute renal reperfusion injury following transient ischemia. We hypothesize that anti-thrombin nanoparticles will ameliorate acute renal injury by inhibiting microvascular thrombosis. Methods: Adult, male Sprague Dawley rats were randomized into two groups of 5 to receive tail vein injections of saline or nanoparticles loaded with Phe[D]-Pro-Arg-Chloromethylketone (NP-PPACK). Immediately following injection, all animals underwent operative bilateral renal artery occlusion to create 45 minutes of warm ischemia, followed by restoration of renal blood flow. Blood samples were drawn daily and animals were euthanized on day 1 or 7 for histologic analysis of kidney injury (H&E, TUNEL and thrombin staining). Results: Histologic analysis of renal tissue revealed significant apoptosis, necrosis and thrombin accumulation 1 day after ischemia-reperfusion, confirming acute kidney injury. The peak creatinine (mg/dl) on day 1 was significantly lower in NP-PPACK treated animals (0.57 +/- 0.07 (SEM)) than in saline treated controls (1.40 +/- 0.20 (SEM); p-value <0.01). Furthermore, animals treated with NP-PPACK continued to exhibit less renal dysfunction for 7 days after injury (Figure 1). Conclusion: Histologically confirmed intrarenal thrombosis was detected one day after ischemia-reperfusion injury. Targeted inhibition of thrombin with NP-PPACK prevented a decline in renal function following transient occlusion. Future work will focus on defining the underlying mechanisms of this effect.

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