The Division of Cardiovascular and Thoracic Surgery, Rabin Medical Center, Petach-Tikva 4941492, Israel.
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
Int J Mol Sci. 2023 Oct 19;24(20):15376. doi: 10.3390/ijms242015376.
This study investigated modifications to the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. mice heart tissues were compared with mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of mice with decreased levels of mRNA and increased levels of , indicating potential cardiac dysfunction. The mRNA levels of (deubiquitinating enzyme), , and (proteasome β-subunits) were down-regulated in mice, while the mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were down-regulated in mice, and RNF167 was elevated in diabetic mice. The reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to the future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.
本研究探讨了 2 型糖尿病（T2DM）小鼠模型中泛素蛋白酶体系统（UPS）的修饰及其与心脏并发症的关系。通过 RNA 测序、qRT-PCR 和蛋白质分析，比较了 型糖尿病小鼠和 型糖尿病小鼠的心脏组织，以鉴定与糖尿病相关的心脏 UPS 修饰。研究结果揭示了 型糖尿病小鼠心脏中存在独特的基因谱，其 mRNA 水平降低， 和 水平升高，表明可能存在心脏功能障碍。 型糖尿病小鼠的 （去泛素化酶）、 、 和 （蛋白酶体β亚基）mRNA 水平下调，而 RNF167（E3 连接酶）的 mRNA 水平升高。相应的 LMP2 和 LMP7 蛋白在 型糖尿病小鼠中下调，而 RNF167 在糖尿病小鼠中升高。LMP2 和 LMP7 的表达减少，以及 RNF167 的表达增加，可能导致糖尿病中常见的未来心脏恶化。本研究提高了我们对糖尿病小鼠心脏 UPS 失衡的理解，并提出了 UPS 与自噬等其他细胞过程相互作用的问题。在这一领域的进一步探索可能为糖尿病心脏并发症的机制和潜在治疗靶点提供有价值的见解。
