Renal fibrosis is characterized by the excessive deposition of extracellular matrix that destroys and replaces the functional renal parenchyma, ultimately leading to organ failure. It is a common pathway by which chronic kidney disease can develop into end-stage renal disease, which has high global morbidity and mortality, and there are currently no good therapeutic agents available. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been indicated to be closely related to the occurrence of renal fibrosis, and its specific inhibitory peptide, autocamtide-2-related inhibitory peptide (AIP), was shown to directly bind the active site of CaMKII. In this study, we examined the effect of AIP on the progression of renal fibrosis and its possible mechanism. The results showed that AIP could inhibit the expression of the fibrosis markers fibronectin, collagen I, matrix metalloproteinase 2, and α-smooth muscle actin in vivo and in vitro. Further analysis revealed that AIP could inhibit the expression of various epithelial-to-mesenchymal transformation-related markers, such as vimentin and Snail 1, in vivo and in vitro. Mechanistically, AIP could significantly inhibit the activation of CaMKII, Smad 2, Raf, and extracellular regulated protein kinases (ERK) in vitro and in vivo and reduce the expression of transforming growth factor-β (TGF-β) in vivo. These results suggested that AIP could alleviate renal fibrosis by inhibiting CaMKII and blocking activation of the TGF-β/Smad2 and RAF/ERK pathways. Our study provides a possible drug candidate and demonstrates that CaMKII is a potential pharmacological target for the treatment of renal fibrosis.

肾纤维化的特点是细胞外基质过度沉积，破坏并取代有功能的肾实质，最终导​​致器官衰竭。它是慢性肾脏病发展为终末期肾病的常见途径，全球发病率和死亡率较高，目前尚无良好的治疗药物。钙/钙调蛋白依赖性蛋白激酶II（CaMKII）已被证明与肾纤维化的发生密切相关，其特异性抑制肽——autocamtide-2相关抑制肽（AIP）被证明可以直接结合活性位点CaMKII 的。在本研究中，我们探讨了AIP对肾纤维化进展的影响及其可能的机制。体内和体外的α-平滑肌肌动蛋白。进一步分析表明，AIP在体内和体外均可抑制波形蛋白和Snail 1等多种上皮间质转化相关标志物的表达。从机制上讲，AIP在体外和体内均能显着抑制CaMKII、Smad 2、Raf和细胞外调节蛋白激酶（ERK）的激活，并降低体内转化生长因子-β（TGF- β）的表达。这些结果表明AIP可以通过抑制CaMKII和阻断TGF- β的激活来减轻肾纤维化/Smad2 和 RAF/ERK 途径。我们的研究提供了一种可能的候选药物，并证明 CaMKII 是治疗肾纤维化的潜在药理学靶点。