Analysis of mRNA and protein kidney injury Molecule-1 (KIM-1) expression in a kidney model during the initiation phase of ischemia reperfusion injury

Dase, Jerny; Rasyid, Haerani; Masadah, Rina; Cangara, Muhammad Husni; Bukhari, Agussalim; Dwiyanti, Ressy; Hatta, Mochammad

doi:10.1016/j.amsu.2022.103373

Cited by 5 publications

(4 citation statements)

References 35 publications

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“…Compared to WT mice that received CIRP, TREM-1 −/− mice had a 33.6% reduction in serum BUN and a 55.4% reduction in serum creatinine ( Figures 2A,B ). Renal mRNA expression of KIM-1, another marker of AKI ( Dase et al, 2022 ), was evaluated in the kidneys of TREM-1 −/− mice and was noted to have a 47.1% decrease compared to WT mice ( Figure 2C ). Additionally, after rmCIRP injection, TREM-1 −/− mice had a 41.6% reduction in renal tissue NGAL mRNA expression and a 38.3% decrease in serum NGAL compared to WT mice ( Figures 2D,E ).…”

Section: Resultsmentioning

confidence: 99%

Extracellular CIRP induces acute kidney injury via endothelial TREM-1

Siskind

Zhang²,

Wang³

2022

Front. Physiol.

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Introduction: Acute kidney injury is associated with elevated serum levels of extracellular cold-inducible RNA-binding protein (eCIRP), a damage-associated molecular pattern released during ischemia/reperfusion injury, hemorrhagic shock, and sepsis. It is unknown if circulating eCIRP and eCIRP-induced activation of receptor triggering receptor expressed on myeloid cells-1 (TREM-1), expressed on endothelial cells, play an important role in the pathogenesis of AKI.Methods: Male B6 wild-type (WT) and TREM-1−/− mice were subjected to intravenous injection of recombinant murine (rm) CIRP. Serum, urine, and renal tissue were collected 6 h later for analysis. Additionally, primary human renal glomerular endothelial cells (HRGEC) were stimulated in vitro with rmCIRP after pretreatment with M3, a novel inhibitory peptide of TREM-1, or vehicle. Supernatants and cells were collected 20 h after stimulation.Results: After injection with rmCIRP, WT mice had a significant increase in serum levels of BUN, creatinine, and NGAL compared to control. Additionally, NGAL was significantly increased in the urine of rmCIRP-injected mice, suggesting that circulating eCIRP can directly induce AKI. The levels of TREM-1 mRNA in the kidneys, as well as soluble (s) TREM-1 released into the serum and urine, were significantly increased in rmCIRP-injected mice. TREM-1−/− mice injected with rmCIRP had attenuated AKI, indicated by significantly decreased serum BUN, creatinine, and NGAL, and renal mRNA expression of NGAL and KIM-1 compared to WT mice. TREM-1−/− mice also had attenuated endothelial activation, with decreased mRNA and protein expression of ICAM-1 in renal tissue. HRGEC stimulated with rmCIRP in vitro had significant increases in cytokine production and sTREM-1 release, which was attenuated in cells treated with M3.Conclusion: Activation of renal TREM-1 with circulating eCIRP is sufficient to cause AKI. Elevated levels of eCIRP may be critical for the development of AKI under conditions such as ischemia/reperfusion injury, hemorrhagic shock, and sepsis. Mice deficient in the TREM-1 receptor have attenuated AKI and reduced endothelial cell activation after injection of rmCIRP. TREM-1 inhibition with M3 attenuates HRGEC activation after eCIRP stimulation. Targeting eCIRP activation of TREM-1 may provide a novel and effective treatment for AKI.

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Section: Resultsmentioning

confidence: 99%

Extracellular CIRP induces acute kidney injury via endothelial TREM-1

Siskind

Zhang²,

Wang³

2022

Front. Physiol.

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“…NGAL levels have also been shown to be highly predictive of AKI in emergency room patients and cardiac surgery patients [42,43]. Studies have shown that KIM-1 mRNA and protein levels are significantly increased in the kidney after ischemia [11,44,45]. In the toxicity models of cisplatin, gentamicin and cyclosporine, KIM-1 significantly outperformed Scr and BUN as an early marker [46].…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid A Improves Rat Kidney Injury by Regulating MAPKs and TGF-β1/Smads Signaling Pathways

et al. 2023

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Salvianolic acid A (SAA) is one of the major components in Salvia miltiorrhiza Bge., with various pharmacological activities, and is likely to be a promising agent for the treatment of kidney diseases. The purpose of this study was to explore the protective effect and mechanisms of SAA on kidney disease. In this study, the improvement effects of SAA (10, 20, 40 mg/kg, i.g.) on kidney injury rats were investigated by detecting the levels of KIM-1, NGAL in serum and UP in the urine of AKI model rats established with gentamicin, as well as the levels of SCr and UREA in serum and IL-6, IL-12, MDA and T-SOD in the kidneys of CKD model rats established with 5/6 nephrectomy. HE and Masson staining were used to observe the histopathological changes in the kidney. Network pharmacology and Western blotting were used to explore the mechanism of SAA in improving kidney injury. The results showed that SAA improved kidney function in kidney injury rats by reducing the kidney index and pathological injury by HE and Masson staining, reducing the levels of KIM-1, NGAL and UP in AKI rats and UREA, SCr and UP in CKD rats, as well as exerting anti-inflammatory and anti-oxidative stress effects by inhibiting the release of IL-6 and IL-12, reducing MDA and increasing T-SOD. Western blotting results showed that SAA significantly reduced the phosphorylation levels of ERK1/2, p38, JNK and smad2/3, and the expression of TLR-4 and smad7. In conclusion, SAA plays a significant role in improving kidney injury in rats and the mechanism may be achieved by regulating the MAPKs and TGF-β1/smads signaling pathways.

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“…KIM-1 is a type I transmembrane glycoprotein that is expressed in the apical membrane of proximal renal tubule cells [68]. This biomarker is characterized by appearing 12-24 h after the onset of the injury [67], relating to the severity of the infection [69]. In a study in Sri Lanka, KIM-1 was detected on the third day of fever after admission and was at its highest concentration on the ninth day [63].…”

Section: Cellular Immunoglobulin Mucin Domain 1 (Kim-1)mentioning

confidence: 99%

Acute Kidney Injury Associated with Severe Leptospirosis: Fatal Re-Emerging Disease in Latin America

Osorio-Rodríguez,

Rodelo-Barrios,

Rebolledo-Maldonado

et al. 2024

Kidney and Dialysis

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Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases, it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America.

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Analysis of mRNA and protein kidney injury Molecule-1 (KIM-1) expression in a kidney model during the initiation phase of ischemia reperfusion injury

Cited by 5 publications

References 35 publications

Extracellular CIRP induces acute kidney injury via endothelial TREM-1

Extracellular CIRP induces acute kidney injury via endothelial TREM-1

Salvianolic Acid A Improves Rat Kidney Injury by Regulating MAPKs and TGF-β1/Smads Signaling Pathways

Acute Kidney Injury Associated with Severe Leptospirosis: Fatal Re-Emerging Disease in Latin America

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