Faculty of Pharmacy, Kindai University, Higashi-Osaka 577-8502, Japan.
Laboratory of Molecularbiology and Histochemistry, Fujita Health University Institute of Joint Research, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi 470-1192, Japan.
Int J Mol Sci. 2018 Nov 18;19(11):3635. doi: 10.3390/ijms19113635.
Diabetes mellitus is a widespread metabolic disorder, and long-term hyperglycemia in diabetics leads to diabetic keratopathy. In the present study, we used a shotgun liquid chromatography/mass spectrometry-based global proteomic approach using the cornea of streptozotocin-induced diabetic (STZ) rats to examine the mechanisms of delayed corneal wound healing in diabetic keratopathy. Applying a label-free quantitation method based on spectral counting, we identified 188 proteins that showed expression changes of >2.0-fold in the cornea of STZ rats. In particular, the level of lumican expression in the cornea of STZ rats was higher than that of the normal rats. In the cornea of the normal rat, the expression level of lumican was elevated during the wound healing process, and it returned to the same expression level as before cornea injury after the wound was healed completely. On the other hand, a high expression level of lumican in the cornea of STZ rats was still maintained even after the wound was healed completely. In addition, adhesion deficiency in corneal basal cells and Bowman's membrane was observed in the STZ rat. Thus, abnormally overexpressed lumican may lead to adhesion deficiency in the cornea of STZ rats.
糖尿病是一种广泛存在的代谢紊乱疾病，糖尿病患者的长期高血糖会导致糖尿病性角膜病变。在本研究中，我们使用基于 shotgun 液相色谱/质谱的全局蛋白质组学方法，对链脲佐菌素（STZ）诱导的糖尿病（STZ）大鼠的角膜进行研究，以探讨糖尿病性角膜病变中角膜愈合延迟的机制。应用基于谱计数的无标记定量方法，我们鉴定出 188 种在 STZ 大鼠角膜中表达变化超过 2.0 倍的蛋白质。特别是，STZ 大鼠角膜中 lumican 的表达水平高于正常大鼠。在正常大鼠的角膜中，lumican 的表达水平在伤口愈合过程中升高，并且在完全愈合后，它恢复到与角膜损伤前相同的表达水平。另一方面，STZ 大鼠角膜中 lumican 的高表达水平甚至在伤口完全愈合后仍保持不变。此外，在 STZ 大鼠中观察到角膜基底细胞和 Bowman 膜的黏附缺失。因此，异常过表达的 lumican 可能导致 STZ 大鼠角膜的黏附缺失。
