Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea.
Functional Cellular Networks Laboratory, Department of Medicine, College of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Int J Mol Sci. 2021 Apr 19;22(8):4230. doi: 10.3390/ijms22084230.
Hypertension induces renal fibrosis or tubular interstitial fibrosis, which eventually results in end-stage renal disease. Epithelial-to-mesenchymal transition (EMT) is one of the underlying mechanisms of renal fibrosis. Though previous studies showed that Ecklonia cava extracts (ECE) and dieckol (DK) had inhibitory action on angiotensin (Ang) I-converting enzyme, which converts Ang I to Ang II. It is known that Ang II is involved in renal fibrosis; however, it was not evaluated whether ECE or DK attenuated hypertensive nephropathy by decreasing EMT. In this study, the effect of ECE and DK on decreasing Ang II and its down signal pathway of angiotensin type 1 receptor (AT1R)//, which is related with the EMT and restoring renal function in spontaneously hypertensive rats (SHRs), was investigated. Either ECE or DK significantly decreased the serum level of Ang II in the SHRs. Moreover, the renal expression of AT1R// was decreased by the administration of either ECE or DK. The mesenchymal cell markers in the kidney of SHRs was significantly decreased by ECE or DK. The fibrotic tissue of the kidney of SHRs was also significantly decreased by ECE or DK. The ratio of urine albumin/creatinine of SHRs was significantly decreased by ECE or DK. Overall, the results of this study indicate that ECE and DK decreased the serum levels of Ang II and expression of AT1R//, and then decreased the EMT and renal fibrosis in SHRs. Furthermore, the decrease in EMT and renal fibrosis could lead to the restoration of renal function. It seems that ECE or DK could be beneficial for decreasing hypertensive nephropathy by decreasing EMT and renal fibrosis.
高血压可引起肾纤维化或肾小管间质纤维化，最终导致终末期肾病。上皮间质转化（EMT）是肾纤维化的潜在机制之一。尽管先前的研究表明，裙带菜提取物（ECE）和二酮（DK）对血管紧张素（Ang）I 转化酶具有抑制作用，该酶将 Ang I 转化为 Ang II。已知 Ang II 参与肾纤维化，但尚未评估 ECE 或 DK 是否通过减少 EMT 来减轻高血压肾病。在这项研究中，研究了 ECE 和 DK 通过减少 Ang II 及其下游信号通路血管紧张素 1 型受体（AT1R）//，从而减轻自发性高血压大鼠（SHR）中 EMT 和恢复肾功能的作用。ECE 或 DK 均可显著降低 SHR 血清中 Ang II 的水平。此外，ECE 或 DK 可降低肾脏中 AT1R//的表达。ECE 或 DK 可显著降低 SHR 肾脏中的间充质细胞标志物。ECE 或 DK 还可显著减少 SHR 肾脏中的纤维化组织。ECE 或 DK 可显著降低 SHR 的尿白蛋白/肌酐比值。总的来说，这项研究的结果表明，ECE 和 DK 降低了血清 Ang II 水平和 AT1R//的表达，从而减少了 SHR 的 EMT 和肾纤维化。此外，EMT 和肾纤维化的减少可能导致肾功能的恢复。似乎 ECE 或 DK 通过减少 EMT 和肾纤维化对降低高血压肾病有益。
