The Effect of Regulating miR-223 Expression on the Expression of Inflammatory Factors and Renal Interstitial Fibrosis in a Rat Model of Chronic Glomerulonephritis and its Relationship with the IL-6/STAT3 Signaling Pathway
LIN Zheng
Longyan First Affiliated Hospital of Fujian Medical University,Longyan Fujian Province 364000, China
The Effect of Regulating miR-223 Expression on the Expression of Inflammatory Factors and Renal Interstitial Fibrosis in a Rat Model of Chronic Glomerulonephritis and its Relationship with the IL-6/STAT3 Signaling Pathway
LIN Zheng
Longyan First Affiliated Hospital of Fujian Medical University,Longyan Fujian Province 364000, China
摘要Objective: To explore the effect of miR-223 on the expression of inflammatory factors and renal interstitial fibrosis in a rat model of chronic glomerulonephritis based on the interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway. Methods:A total of 70 SPF-grade healthy adult male SD rats were selected, and were randomly divided into five groups. Except for the blank group, the remaining four groups of rats were all subcutaneously injected with 1 mg/mL cationized bovine serum albumin (C-BSA) emulsion at multiple points (in the first week) and injected with 2.5 mg/mL C-BSA solution through the tail vein (from the 2nd to 4th week) to establish a glomerulonephritis model. After successful modeling, the blank group and the modeling group were injected with normal saline through the tail vein, the negative control group was injected with 50 μg/kg NC agomir through the tail vein, the miR-223 agonist group was injected with 50 μg/kg miR-223 agomir through the tail vein, and the pathway activation group was injected with 50 μg/kg miR-223 agomir and 1 μg/kg rhIL-6 through the tail vein. After continuous treatment for 21 d, the rats were sacrificed and kidney tissues were taken. The expression of miR-223, inflammatory factors and IL-6/STAT3 signaling pathway-related proteins in the five groups of rats was observed and compared, and the renal interstitial fibrosis in the five groups of rats was also observed and compared. Results:The relative expression level of miR-223 in the blank group was significantly higher than that in the other four groups. The relative expression levels of miR-223 in the miR-223 agonist group and the pathway activation group were significantly higher than those in the model group and the negative control group (P<0.05). The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the blank group were lower than those in the other four groups. The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the pathway activation group were higher than those in the miR-223 agonist group (P<0.05). The proportion of renal interstitial fibrosis area in renal tissue of the blank group was significantly lower than that in the other four groups. The proportion of renal interstitial fibrosis area in renal tissue of the model group and the negative control group was higher than that in the miR-223 agonist group and the pathway activation group. The proportion of renal interstitial fibrosis area in renal tissue of the pathway activation group was higher than that in the miR-223 agonist group (P<0.05). The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the blank group were lower than those in the other four groups. The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the pathway activation group were higher than those in the miR-223 agonist group (P<0.05). Conclusion:The expression of inflammatory factors and renal interstitial fibrosis in rats with chronic glomerulonephritis are affected by miR-223. The mechanism may be related to the expression of IL-6/STAT3 signaling pathway-related proteins.
Abstract：Objective: To explore the effect of miR-223 on the expression of inflammatory factors and renal interstitial fibrosis in a rat model of chronic glomerulonephritis based on the interleukin 6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling pathway. Methods:A total of 70 SPF-grade healthy adult male SD rats were selected, and were randomly divided into five groups. Except for the blank group, the remaining four groups of rats were all subcutaneously injected with 1 mg/mL cationized bovine serum albumin (C-BSA) emulsion at multiple points (in the first week) and injected with 2.5 mg/mL C-BSA solution through the tail vein (from the 2nd to 4th week) to establish a glomerulonephritis model. After successful modeling, the blank group and the modeling group were injected with normal saline through the tail vein, the negative control group was injected with 50 μg/kg NC agomir through the tail vein, the miR-223 agonist group was injected with 50 μg/kg miR-223 agomir through the tail vein, and the pathway activation group was injected with 50 μg/kg miR-223 agomir and 1 μg/kg rhIL-6 through the tail vein. After continuous treatment for 21 d, the rats were sacrificed and kidney tissues were taken. The expression of miR-223, inflammatory factors and IL-6/STAT3 signaling pathway-related proteins in the five groups of rats was observed and compared, and the renal interstitial fibrosis in the five groups of rats was also observed and compared. Results:The relative expression level of miR-223 in the blank group was significantly higher than that in the other four groups. The relative expression levels of miR-223 in the miR-223 agonist group and the pathway activation group were significantly higher than those in the model group and the negative control group (P<0.05). The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the blank group were lower than those in the other four groups. The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-1β, IL-17, TNF-α, and TGF-β1 in the pathway activation group were higher than those in the miR-223 agonist group (P<0.05). The proportion of renal interstitial fibrosis area in renal tissue of the blank group was significantly lower than that in the other four groups. The proportion of renal interstitial fibrosis area in renal tissue of the model group and the negative control group was higher than that in the miR-223 agonist group and the pathway activation group. The proportion of renal interstitial fibrosis area in renal tissue of the pathway activation group was higher than that in the miR-223 agonist group (P<0.05). The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the blank group were lower than those in the other four groups. The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the model group and the negative control group were significantly higher than those in the miR-223 agonist group and the pathway activation group. The expression levels of IL-6/GAPDH and p-STAT3/STAT3 in the pathway activation group were higher than those in the miR-223 agonist group (P<0.05). Conclusion:The expression of inflammatory factors and renal interstitial fibrosis in rats with chronic glomerulonephritis are affected by miR-223. The mechanism may be related to the expression of IL-6/STAT3 signaling pathway-related proteins.
LIN Zheng. The Effect of Regulating miR-223 Expression on the Expression of Inflammatory Factors and Renal Interstitial Fibrosis in a Rat Model of Chronic Glomerulonephritis and its Relationship with the IL-6/STAT3 Signaling Pathway[J]. 中国生物医学工程学报(英文版）, 2024, 33(3): 107-114.
LIN Zheng. The Effect of Regulating miR-223 Expression on the Expression of Inflammatory Factors and Renal Interstitial Fibrosis in a Rat Model of Chronic Glomerulonephritis and its Relationship with the IL-6/STAT3 Signaling Pathway. Chinese Journal of Biomedical Engineering, 2024, 33(3): 107-114.
[1] Hu J, Ke R, Teixeira W, et al.Global, regional, and national burden of CKD due to glomerulonephritis from 1990 to 2019: A systematic analysis from the global burden of disease study 2019[J]. Clin J Am Soc Nephrol, 2023, 18(1): 60-71. [2] Ali M, Esfandyari S, Al-Hendy A.Evolving role of microRNAs in uterine fibroid pathogenesis: filling the gap[J]. Fertil Steril, 2020, 113(6): 1167-1168. [3] Wang L, Lin J, Yu T, et al.Identification of plasma miR-106a-5p and miR-30a-5p as potential biomarkers for mesangial proliferative glomerulonephritis[J]. Clin Biochem, 2020, 84: 79-86. [4] Hejazian SM, Ardalan M, Shoja MM, et al.Expression levels of miR-30c and miR-186 in adult patients with membranous glomerulonephritis and focal segmental glomerulosclerosis[J]. Int J Nephrol Renovasc Dis, 2020, 13: 193-201. [5] Abdul-Maksoud RS, Rashad NM, Elsayed WSH, et al.Circulating miR-181a and miR-223 expression with the potential value of biomarkers for the diagnosis of systemic lupus erythematosus and predicting lupus nephritis[J]. J Gene Med, 2021, 23(5): e3326. [6] Song J, Qin X, Li H, et al.Clinical and pathological correlation between urinary exosome miR-223 and IgAN patients[J]. Clin Nephrol, 2023, 100(5): 209-215. [7] Fourdinier O, Schepers E, Metzinger-Le Meuth V, et al. Serum levels of miR-126 and miR-223 and outcomes in chronic kidney disease patients[J]. Sci Rep, 2019, 9(1): 4477. [8] Ashall V, Morton D, Clutton E.A Declaration of Helsinki for animals[J]. Vet Anaesth Analg, 2023, 50(4): 309-314. [9] Djudjaj S, Boor P.Cellular and molecular mechanisms of kidney fibrosis[J]. Mol Aspects Med, 2019, 65: 16-36. [10] Zhang QB, Zhu D, Dai F, et al.MicroRNA-223 suppresses IL-1β and TNF-α production in gouty inflammation by targeting the NLRP3 inflammasome[J]. Front Pharmacol, 2021, 12: 637415. [11] Yang QB, Li LQ, Zhang QB, et al.microRNA-223 deficiency exacerbates acute inflammatory response to monosodium urate crystals by targeting NLRP3[J]. J Inflamm Res, 2021, 14: 1845-1858. [12] Róka B, Tod P, Kaucsár T, et al.Delayed contralateral nephrectomy halted post-ischemic renal fibrosis progression and inhibited the ischemia-induced fibromir upregulation in mice[J]. Biomedicines, 2021, 9(7): 815. [13] Chen Q, Wang H, Liu Y, et al.Inducible microRNA-223 down-regulation promotes TLR-triggered IL-6 and IL-1β production in macrophages by targeting STAT3[J]. PLoS One, 2012, 7(8): e42971.
