Increased fibrotic signaling in a murine model for intra-arterial contrast-induced acute kidney injury

Abstract

Contrast-induced acute kidney injury (CI-AKI) is a vexing problem, and more than 70 million patients undergo studies using iodinated contrast. The molecular mechanisms responsible for CI-AKI are poorly understood. The goal of the present article was to determine the role of transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog (SMAD)3 and associated collagen expression in a murine model of intra-arterial CI-AKI. The murine model of CI-AKI after intra-arterial contrast agent administration was created by first performing a partial nephrectomy to induce chronic kidney disease. Twenty-eight days later, 100 μL of contrast agent [iodixanol (320 mg/mL)] or saline were administered via the carotid artery. Two days after contrast administration, compared with saline, average serum creatinine was significantly elevated ( P < 0.05). In the cortex, there was a significant increase in phosphorylated SMAD3 and gene expression of TGF-β1, TGF-β receptor type I, and TGF-β receptor type II at day 2 in the contrast group compared with the saline group. Average gene expressions of connective tissue growth factor, matrix metalloproteinase-2 and −9, and collagen type I-α and type IV-α were significantly increased at 2 days after contrast administration (all P < 0.05). Moreover, there was a decrease in Ki-67 staining in the cortex, with an increase in terminal deoxynucleotidyl transferase dUTP nick-end labeling in the cortex and medulla after contrast administration ( P < 0.05). In the murine intra-arterial CI-AKI model, there was increased hypoxia and TGF-β1/SMAD3 pathway activation and collagen expression, resulting in renal fibrosis. Together, these results suggest that the TGF-β1/SMAD3 pathway could be a potential target in alleviating tissue fibrosis in CI-AKI.

Establishment and assessment of a preclinical model of acute kidney injury induced by contrast media combined acute myocardial ischemia reperfusion surgery

“…All the rats were dehydrated 24 h before surgery as a pre-treating procedure. Consistent with previous research, the model of contrast media after dehydration alone had a low postoperative AKI rate of around 30% ( 19 ). Given extended postoperative nursing time increases rat mortality, we collected blood, heart, and kidney 24 h following surgery.…”

Assessment of Fasudil on Contrast-Associated Acute Kidney Injury Using Multiparametric Renal MRI

“…Research increasingly tends to support the view that renal fibrosis in the course of long-term CA-AKI is inflicted by a host of insults, for instance, stress molecules and growth factors ( Sharma et al, 2020 ). The process of renal fibrosis has several crucial phases, including excessive and progressive accumulation of extracellular matrix (ECM), activation of renal interstitial fibroblasts, EMT, and inflammatory cell infiltration ( Ferenbach and Bonventre 2015 ).…”