Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Jan 5;13(2):2885-2894.
doi: 10.18632/aging.202381. Epub 2021 Jan 5.

Serum response factor, a novel early diagnostic biomarker of acute kidney injury

Long Zhao  1 , Chenyu Li  1 , Chen Guan  1 , Ning Song  2 , Hong Luan  1 , Congjuan Luo  1 , Wei Jiang  1 , Quandong Bu  1 , Yanfei Wang  1 , Lin Che  1 , Yan Xu  1
Affiliations

Serum response factor, a novel early diagnostic biomarker of acute kidney injury

Long Zhao et al. Aging (Albany NY). .

Abstract

Objective: Studies have shown that serum response factor (SRF) is increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic value of SRF in acute kidney injury (AKI).

Methods: AKI-related microarray data were analyzed, and the expression and location of SRF were investigated in the early phase of AKI.

Results: Bioinformatics results demonstrated that SRF was dramatically elevated 2-4 h after ischemia/reperfusion (I/R) in mouse renal tissue. In I/R rats, SRF was mostly expressed and located in renal tubular epithelial cells (TECs). SRF started to increase at 1 h, peaked at 3-9 h and started to decrease at 12 h after I/R. The areas under the ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and serum creatinine (Scr) were 87.9%, 83.0%, 81.3%, 78.8%, 68.8%, respectively.

Conclusion: SRF is remarkably upregulated in early (before 24 h) AKI and can replace Scr as a potential new early diagnostic biomarker of AKI.

Keywords: acute kidney injury; biomarker; serum response factor.

PubMed Disclaimer

Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
Analysis of the microarray results from bilateral I/R mice. (A, B) Gene expression profiling of kidney at 2 h and 4 h after I/R compared with the control group. Volcano plot of log2 fold changes versus -log10 FDR showed transcriptional differences between the I/R group and the control group. Vertical dashed lines denote the cutoff of 2-fold change, and the horizontal dashed line represents the 0.05 FDR cutoff. SRF was increased after 2 h renal I/R in mice (fold change>2, FDR<0.05). (C) SRF expression in I/R kidneys at 2 h, 4 h, 24 h, 48 h, 72 h, 7 d, 14 d, 28 d, 6 m and 12 m. Data are expressed as the mean ± SE. *FDR<0.05 (linear models for microarray analysis) versus the control group.
Figure 2
Figure 2
SRF was upregulated and localized in TECs in I/R rats. Location of SRF in kidney 6 h after I/R as evidenced by IHC and IF staining. Data are representative of at least three separate experiments.
Figure 3
Figure 3
Scr level and renal SRF mRNA expression in I/R rats. (A) mRNA expression of SRF in I/R kidneys. The trend line was calculated by local polynomial regression fitting. (B) Scr levels in I/R rats. Data are expressed as the mean ± SE (N=7 in each group). *P<0.05 versus the sham group, #P<0.05 versus the control group. Data are representative of at least three separate experiments.
Figure 4
Figure 4
The protein level of SRF in kidney, urine and serum in vivo. (A, B) Protein expression level of SRF in kidney as measured by western blot and quantitative analyses. (C) The expression of SRF in serum. (D) The expression of SRF in urine. The trend line was calculated by local polynomial regression fitting. Data are expressed as the mean ± SE (N=7 in each group). *P<0.05 versus the sham group, #P<0.05 versus the control group.
Figure 5
Figure 5
The ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and Scr in early (before 24 h) AKI. (A–E) The measured values (SRF mRNA, SRF protein, urinary SRF, serum SRF and Scr) of the AKI group (all time points after AKI as one group) were compared to those of the control group. The cutoff thresholds represent the fold change in measured values in the AKI group compared with the control group.
See this image and copyright information in PMC

References

    1. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012; 120:c179–84. 10.1159/000339789 - DOI - PubMed
    1. Pan HC, Wu PC, Wu VC, Yang YF, Huang TM, Shiao CC, Chen TC, Tarng DC, Lin JH, Yang WS, Sun CY, Lin CY, Chu TS, et al. , and Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs). A nationwide survey of clinical characteristics, management, and outcomes of acute kidney injury (AKI) - patients with and without preexisting chronic kidney disease have different prognoses. Medicine (Baltimore). 2016; 95:e4987. 10.1097/MD.0000000000004987 - DOI - PMC - PubMed
    1. Havasi A, Borkan SC. Apoptosis and acute kidney injury. Kidney Int. 2011; 80:29–40. 10.1038/ki.2011.120 - DOI - PMC - PubMed
    1. Ho PW, Pang WF, Szeto CC. Remote ischaemic pre-conditioning for the prevention of acute kidney injury. Nephrology (Carlton). 2016; 21:274–85. 10.1111/nep.12614 - DOI - PubMed
    1. Tennankore KK, Kim SJ, Alwayn IP, Kiberd BA. Prolonged warm ischemia time is associated with graft failure and mortality after kidney transplantation. Kidney Int. 2016; 89:648–58. 10.1016/j.kint.2015.09.002 - DOI - PubMed

Publication types

Substances

LinkOut - more resources