Cysteine‐rich protein 61, a specific ultra‐early biomarker in kidney ischemia/reperfusion injury

Abstract

Aim: Studies have shown that cysteine-rich protein 61 (Cyr61) increased in the post-ischemic human kidney tissue. However, it is still unknown whether Cyr61 can be used as a biomarker in kidney ischemia/reperfusion (I/R) injury.Methods: Microarray data were collected from GSE58438 and GSE52004.The rat I/R model was established to evaluate the messenger RNA and protein expression of Cyr61, localization of Cyr61 by immunohistochemical and immunofluorescence staining, and changes in serum creatinine (Scr) at the same time.Results: Bioinformatics result showed that Cyr61 was significantly increased at 3 h after I/R in rat kidney, and involved in angiogene, positive regulation of locomotion and single organism cell adhesion. The rat I/R model results showed that Cyr61 was mainly expressed in renal tubular epithelial cells with I/R injury and the expression of Cyr61 was upregulated at I/R 1 h, peaked at 4-8 h and began to decay at 12 h. The area under curve of receiver operating characteristics of kidney tissue Cyr61 messenger RNA and urine Cyr61 were 90.2% and 86.1%, which all better than Scr 67.1% (P < 0.05). Conclusion:We made a preliminary investigation of the relationship between Cyr61 and AKI, which identifies that Cyr61 may replace Scr as an ultra-early new biomarker in AKI.

Role of promoting inflammation of Krüppel-like factor 6 in acute kidney injury

“…However, they all have a certain hysteresis and a lack of specificity, which are unable to identify the ultra-early stages of renal dysfunction. Therefore, ultra-early indicators are urgently needed for diagnosis of AKI to improve early prevention and treatment [ 36 ]. Our studies have shown that after renal IR injury, the level of Scr reaches the highest at 24 h, pathological damage is also the heaviest, accompanied by infiltration of inflammatory cells and activation of inflammatory cytokines (increased pro-inflammatory cytokines, decreased anti-inflammatory cytokines) [ 37 ].…”

Scutellarin Ameliorates Renal Injury via Increasing CCN1 Expression and Suppressing NLRP3 Inflammasome Activation in Hyperuricemic Mice

“…Considerable studies revealed that CCN1 is an immediate early gene product pertaining to the CCN family (CCN1/Ctgf/Nov family) and also a vascular regulatory factor of extracellular matrix cross-linking (Kleer, 2016;Wu et al, 2016;Yeger and Perbal, 2016). Intriguingly, CCN1 is a key protein in the transition from acute kidney injury (AKI) to CKD, and blockade of CCN1 can mitigate renal inflammation and fibrosis after ischemic reperfusion induced AKI (Lai et al, 2014;Li et al, 2019). Our previous study (Li et al, 2018) showed that as a hub gene, CCN1 overexpressed in CKD based on 373 CKD patient samples.…”

“…The homogenate was centrifuged at 10,000 g for 30 min at 4°C. 50 μg protein in mixture solution were separated with 10% SDS-PAGE and then transferred onto PVDF membranes of 0.45 μm (Millipore, Germany) incubated with 5% skimmed milk in phosphate-buffered saline at room temperature for 1 h (Li et al, 2019). After incubation with primary antibodies against and β-actin (Cell Signaling Technology, MA, United States) overnight at 4°C, the membrane was incubated with secondary antibodies after washing with PBS and Tween 20.…”

“…CCN1 as a cysteine-rich secretory protein promotes embryonic development, adhesion, chemotaxis, cell proliferation, and neovascularization (Lau, 2016), and is increased in inflammation, apoptosis, and other injury conditions (Lai et al, 2013). Our previous studies found that CCN1 showed antiapoptosis effect in ischemic renal tubular epithelial cells (Xu et al, 2014;Li et al, 2019). In this study, we analyzed the effect of scutellarin on HN by using C57BL/6 mice and human renal tubular epithelial cell line HK-2 subjected to adenine/ potassium oxonate and UA to mimic a HN injury.…”

Biomarkers in acute kidney injury

“…Previous studies have detected low levels of Cyr61 expression in the healthy adult kidney, but increased expression in ischemic renal tissue. It is also elevated in in lammatory states, suggesting it may be a potential biomarker for AKI [30,31]. Xu, et al found that Cyr 61 could protect tubular epithelial cells from apoptosis; however, its capability to detect AKI and when it is detected is still unknown [32].…”