Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China.
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
J Zhejiang Univ Sci B. 2024 Apr 15;25(4):341-353. doi: 10.1631/jzus.B2300033.
Kidney fibrosis is an inevitable result of various chronic kidney diseases (CKDs) and significantly contributes to end-stage renal failure. Currently, there is no specific treatment available for renal fibrosis. ELA13 (amino acid sequence: RRCMPLHSRVPFP) is a conserved region of ELABELA in all vertebrates; however, its biological activity has been very little studied. In the present study, we evaluated the therapeutic effect of ELA13 on transforming growth factor-β1 (TGF-β1)-treated NRK-52E cells and unilateral ureteral occlusion (UUO) mice. Our results demonstrated that ELA13 could improve renal function by reducing creatinine and urea nitrogen content in serum, and reduce the expression of fibrosis biomarkers confirmed by Masson staining, immunohistochemistry, real-time polymerase chain reaction (RT-PCR), and western blot. Inflammation biomarkers were increased after UUO and decreased by administration of ELA13. Furthermore, we found that the levels of essential molecules in the mothers against decapentaplegic (Smad) and extracellular signal-regulated kinase (ERK) pathways were reduced by ELA13 treatment in vivo and in vitro. In conclusion, ELA13 protected against kidney fibrosis through inhibiting the Smad and ERK signaling pathways and could thus be a promising candidate for anti-renal fibrosis treatment.
肾纤维化是各种慢性肾脏病（CKD）的必然结果，是导致终末期肾衰竭的主要原因。目前，肾纤维化尚无特异性治疗方法。ELA13（氨基酸序列：RRCMPLHSRVPFP）是所有脊椎动物中 ELABELA 的保守区域；然而，其生物学活性尚未得到充分研究。在本研究中，我们评估了 ELA13 对转化生长因子-β1（TGF-β1）处理的 NRK-52E 细胞和单侧输尿管梗阻（UUO）小鼠的治疗效果。结果表明，ELA13 可通过降低血清肌酐和尿素氮含量改善肾功能，并通过 Masson 染色、免疫组织化学、实时聚合酶链反应（RT-PCR）和 Western blot 证实减少纤维化生物标志物的表达。UUO 后炎症生物标志物增加，而 ELA13 给药后则减少。此外，我们发现 ELA13 处理可降低体内和体外 Smad 和细胞外信号调节激酶（ERK）通路的必需分子水平。综上所述，ELA13 通过抑制 Smad 和 ERK 信号通路来预防肾纤维化，因此可能是一种有前途的抗肾纤维化治疗候选药物。
