Qing Mingjie, Zhang Ximei, Li Qiangxiang, Yan Canqun
Department of Endocrinology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
Department of Nephrology, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, China.
BMC Nephrol. 2025 Apr 17;26(1):196. doi: 10.1186/s12882-025-04050-1.
To elucidate the mechanism by which pancreatic kininogenase (PKase) impacts renal fibrosis in diabetic nephropathy through modulation of the Notch1/Hes1 and Pten/Akt pathways.
This study employed in vivo models and cellular assays to investigate PKase's effects on cellular viability, apoptosis, and oxidative stress. Assay kits were used to assess these parameters, while protein expression levels were measured via Western Blot and RT-qPCR. Histological changes in kidney tissues were analyzed using HE and Masson's staining. Fibrosis markers-including E-cadherin, vimentin, α-SMA, Collagen I, TGF-β, and fibronectin-were evaluated through immunofluorescence and immunohistochemistry.
After eight weeks of PKase treatment, significant improvements in blood glucose levels and associated symptoms were observed in diabetic nephropathy rats. Both in vivo and in vitro results demonstrated that PKase treatment inhibited the expression of diabetic nephropathy markers, including vimentin, α-SMA, FN, Collagen I, and TGF-β, while increasing the expression of E-cadherin. Additionally, the expression of Notch1, Hes1, and phosphorylated Akt (p-Akt) was upregulated, and Pten expression was suppressed, all of which were reversed by PKase treatment. Furthermore, both analyses indicated that PKase alleviated Jagged1-induced apoptosis and oxidative stress, and mitigated tubulointerstitial fibrosis.
PKase appears to ameliorate diabetic nephropathy-induced renal fibrosis by activating the Pten/Akt pathway and inhibiting the Notch1/Hes1 pathway, suggesting its potential as a therapeutic agent in diabetic nephropathy.
Not applicable.
阐明胰激肽原酶（PKase）通过调节Notch1/Hes1和Pten/Akt信号通路影响糖尿病肾病肾纤维化的机制。
本研究采用体内模型和细胞实验来研究PKase对细胞活力、凋亡和氧化应激的影响。使用检测试剂盒评估这些参数，同时通过蛋白质免疫印迹法（Western Blot）和逆转录-定量聚合酶链反应（RT-qPCR）测量蛋白质表达水平。采用苏木精-伊红（HE）染色和Masson染色分析肾组织的组织学变化。通过免疫荧光和免疫组织化学评估纤维化标志物，包括E-钙黏蛋白、波形蛋白、α-平滑肌肌动蛋白（α-SMA）、I型胶原、转化生长因子-β（TGF-β）和纤连蛋白。
PKase治疗8周后，糖尿病肾病大鼠的血糖水平及相关症状有显著改善。体内和体外实验结果均表明，PKase治疗可抑制糖尿病肾病标志物波形蛋白、α-SMA、纤连蛋白、I型胶原和TGF-β的表达，同时增加E-钙黏蛋白的表达。此外，Notch1、Hes1和磷酸化Akt（p-Akt）的表达上调，Pten表达受到抑制，而PKase治疗可逆转这些变化。此外，两项分析均表明，PKase可减轻Jagged1诱导的细胞凋亡和氧化应激，并减轻肾小管间质纤维化。
PKase似乎通过激活Pten/Akt信号通路和抑制Notch1/Hes1信号通路来改善糖尿病肾病诱导的肾纤维化，提示其在糖尿病肾病治疗中的潜在应用价值。
不适用。
