Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 613, Taiwan.
Molecules. 2022 Apr 20;27(9):2644. doi: 10.3390/molecules27092644.
Diabetes-induced chronic kidney disease leads to mortality and morbidity and thus poses a great health burden worldwide. Krüppel-like factor 10 (KLF10), a zinc finger-containing transcription factor, regulates numerous cellular functions, such as proliferation, differentiation, and apoptosis. In this study, we explored the effects of KLF10 on diabetes-induced renal disease by using a KLF10 knockout mice model. Knockout of KLF10 obviously diminished diabetes-induced tumor growth factor-β (TGF-β), fibronectin, and type IV collagen expression, as evidenced by immunohistochemical staining. KLF10 knockout also repressed the expression of Dickkopf-1 (DKK-1) and phosphorylated β-catenin in diabetic mice, as evidenced by immunohistochemical staining and Western blot analysis. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) revealed that significantly decreased type IV collagen, fibronectin, and DKK-1 existed in KLF10 knockout diabetic mice compared with control diabetic mice. Moreover, knockout of KLF10 reduced the renal fibrosis, as shown by Masson's Trichrome analysis. Overall, the results indicate that depletion of KLF10 ameliorated diabetic renal fibrosis via the downregulation of DKK-1 expression and inhibited TGF-β1 and phosphorylated β-catenin expression. Our findings suggest that KLF10 may be a promising therapeutic choice for the treatment of diabetes-induced renal fibrosis.
糖尿病引起的慢性肾病导致死亡率和发病率增加，因此在全球范围内造成了巨大的健康负担。Krüppel 样因子 10（KLF10）是一种含锌指的转录因子，调节多种细胞功能，如增殖、分化和凋亡。在这项研究中，我们通过使用 KLF10 敲除小鼠模型来探讨 KLF10 对糖尿病肾病的影响。免疫组织化学染色表明，KLF10 的敲除明显减少了糖尿病诱导的肿瘤生长因子-β（TGF-β）、纤维连接蛋白和 IV 型胶原的表达。KLF10 的敲除还抑制了糖尿病小鼠中 Dickkopf-1（DKK-1）和磷酸化β-连环蛋白的表达，这一点通过免疫组织化学染色和 Western blot 分析得到证实。定量逆转录聚合酶链反应（RT-PCR）显示，与对照组糖尿病小鼠相比，KLF10 敲除糖尿病小鼠的 IV 型胶原、纤维连接蛋白和 DKK-1 表达明显减少。此外，KLF10 的敲除减少了 Masson 三色分析中的肾纤维化。总的来说，这些结果表明，KLF10 的耗竭通过下调 DKK-1 表达并抑制 TGF-β1 和磷酸化 β-连环蛋白表达，改善了糖尿病肾纤维化。我们的研究结果表明，KLF10 可能是治疗糖尿病诱导的肾纤维化的一种有前途的治疗选择。
