Miny Sarah, Runel Gaël, Chlasta Julien, Bonod Christelle
Skin Functional Integrity Group, Laboratory for Tissue Biology and Therapeutics Engineering (LBTI), CNRS UMR5305, University of Lyon, 7 Passage du Vercors, 69367 Lyon, CEDEX 07, France.
BioMeca, 69008 Lyon, France.
Dermatopathology (Basel). 2025 Jun 17;12(2):18. doi: 10.3390/dermatopathology12020018.
Diabetics accumulate Advanced Glycation End products (AGEs) such as Nε-(carboxymethyl)lysine (CML) in their skin, which can provoke changes in the skin's biomechanical properties. The same changes are also observed during aging. Collagen is one of the first targets of glycation, and this leads to the disruption of the dermis, potentially contributing to the skin complications seen in diabetes, like impaired wound healing and the formation of chronic ulcers. We therefore investigated whether it was possible to detect differences in the biomechanical properties of the reticular dermis by comparing C57/BL6 control mice, type 1 and type 2 diabetic mice, and aged mice.
To investigate this, we used an Atomic Force Microscope (a type of local probe microscope used to visualize the surface topography of a sample) to measure the elastic modulus of each skin sample. The elastic modulus is a parameter that describes a tissue's resistance to elastic deformation when stress is applied. We also determined whether diabetes is associated with the accumulation of AGEs via Western blots.
We found that type 2 diabetic mice and aged mice had a stiffer reticular dermis than young control mice. No differences were found in type 1 diabetic mice. The results of the Western blot did not reveal any significant differences in the CML content in different types of mice, although a non-significant increase was found in type 2 diabetic and aged mice. We show that there is a significant positive correlation between the amount of CML in a mouse and the rigidity of its reticular dermis.
CONCLUSIONS/INTERPRETATION: We have demonstrated that increased glycation in mouse skin is correlated with the biomechanical properties of that skin, which explains the wound healing defects diabetic patient's experience. AFM is therefore a powerful technique that could be used to characterize the mechanical effects of treatments aimed at reducing the level of AGEs in the skin.
糖尿病患者的皮肤中会积累晚期糖基化终末产物（AGEs），如Nε-（羧甲基）赖氨酸（CML），这会引发皮肤生物力学特性的改变。在衰老过程中也会观察到同样的变化。胶原蛋白是糖基化的首要靶点之一，这会导致真皮层遭到破坏，可能引发糖尿病患者出现的皮肤并发症，如伤口愈合受损和慢性溃疡的形成。因此，我们通过比较C57/BL6对照小鼠、1型和2型糖尿病小鼠以及老年小鼠，研究是否能够检测到网状真皮生物力学特性的差异。
为了进行此项研究，我们使用原子力显微镜（一种用于观察样品表面形貌的局部探针显微镜）来测量每个皮肤样本的弹性模量。弹性模量是一个描述组织在受到应力时抵抗弹性变形能力的参数。我们还通过蛋白质免疫印迹法确定糖尿病是否与AGEs的积累有关。
我们发现，2型糖尿病小鼠和老年小鼠的网状真皮比年轻对照小鼠更硬。1型糖尿病小鼠未发现差异。蛋白质免疫印迹结果未显示不同类型小鼠的CML含量有任何显著差异，尽管在2型糖尿病小鼠和老年小鼠中发现有不显著的增加。我们发现小鼠体内CML的含量与其网状真皮的硬度之间存在显著正相关。
结论/解读：我们已经证明，小鼠皮肤中糖基化增加与其皮肤的生物力学特性相关，这解释了糖尿病患者所经历的伤口愈合缺陷。因此，原子力显微镜是一种强大的技术，可用于表征旨在降低皮肤中AGEs水平的治疗的机械效果。
