Xiang M, Wang Y, Mei R, Fu J, Chen J, DU C
Department of Medical Functional Sciences, Medical College of Anhui University of Science & Technology, Huainan 232001, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 May 20;42(5):772-779. doi: 10.12122/j.issn.1673-4254.2022.05.21.
To explore the role of interleukin-17A (IL-17A) in renal epithelial- mesenchymal transition (EMT) in essential hypertensive nephropathy.
Four-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats (control group) were both randomized into 4 groups (=5) for observation at 4, 6, 10 and 30 weeks of age. Blood pressure of the rats was monitored using a noninvasive tail artery blood pressure measurement instrument. The percentage of Th17 cells in the splenocytes was analyzed using flow cytometry. The mRNA and protein expression levels of IL-17A, iNOS, Arg-1, E-cadherin, and α-SMA in the kidneys of the rats were detected using RT-PCR and immunohistochemical staining, respectively, and plasma levels of IL-17A were regularly detected using ELISA.
At the age of 6 weeks, the SHRs began to show significantly higher blood pressure with greater Th17 cell percentage in the splenocytes and high renal expression and plasma level of IL-17A than WKY rats ( < 0.05 or < 0.01). At 30 weeks, renal expression of E-cadherin mRNA and protein was significantly lower and the expression of Arg-1 mRNA and protein was significantly higher in SHR than in WKY rats ( < 0.01). Compared with the WKY rats, the SHRs showed significantly higher mRNA and protein expressions of iNOS at 6 and 10 weeks ( < 0.05 or 0.01) and higher α-SMA mRNA and protein expressions since 10 weeks of age ( < 0.05 or 0.01). In SHRs older than 10 weeks, renal IL-17A mRNA and protein expression levels were negatively correlated with those of E-cadherin (=-0.731, < 0.05; =-0.827, < 0.01) and positively correlated with those of α-SMA (=0.658, < 0.05; =0.968, < 0.01).
IL-17A is closely correlated with the progression of renal EMT in SHR and plays its role possibly by mediating M1/M2 polarization of renal infiltrating macrophages.
探讨白细胞介素-17A(IL-17A)在原发性高血压肾病肾上皮-间质转化(EMT)中的作用。
将4周龄的自发性高血压大鼠(SHR)和Wistar-Kyoto(WKY)大鼠(对照组)均随机分为4组(每组n = 5),分别在4、6、10和30周龄时进行观察。使用无创尾动脉血压测量仪监测大鼠血压。采用流式细胞术分析脾细胞中Th17细胞的百分比。分别采用RT-PCR和免疫组化染色检测大鼠肾脏中IL-17A、诱导型一氧化氮合酶(iNOS)、精氨酸酶-1(Arg-1)、E-钙黏蛋白和α-平滑肌肌动蛋白(α-SMA)的mRNA和蛋白表达水平,并用ELISA法定期检测血浆中IL-17A水平。
6周龄时,SHR的血压开始显著高于WKY大鼠,脾细胞中Th17细胞百分比更高,肾脏中IL-17A的表达及血浆水平也更高(P < 0.05或P < 0.01)。30周时,SHR肾脏中E-钙黏蛋白mRNA和蛋白表达显著低于WKY大鼠,而Arg-1 mRNA和蛋白表达显著高于WKY大鼠(P < 0.01)。与WKY大鼠相比,SHR在6周和10周时iNOS的mRNA和蛋白表达显著更高(P < 0.05或P < 0.01),10周龄后α-SMA的mRNA和蛋白表达更高(P < 0.05或P < 0.01)。在10周龄以上的SHR中,肾脏IL-17A mRNA和蛋白表达水平与E-钙黏蛋白呈负相关(r = -0.731,P < 0.05;r = -0.827,P < 0.01),与α-SMA呈正相关(r = 0.658,P < 0.05;r = 0.968,P < 0.01)。
IL-17A与SHR肾EMT的进展密切相关,可能通过介导肾浸润巨噬细胞的M1/M2极化发挥作用。