Glucosamine mitigates hyperglycemic-induced oxidative stress via the SIRT1 pathway in human corneal epithelial cells.

Hyperglycemia threatens vision via inducing irreversible morphologic and physiologic changes in the corneal epithelium. We aimed to investigate whether glucosamine (GlcN) is capable of countering the detrimental effects of high glucose (HG) levels on human corneal epithelial (HCE-T) cells. GlcN failed to attenuate the HG-associated cytotoxicity in HCE-T cells owing to its inherent cytotoxicity. Compared with the decrease in the pAKT/AKT and p-p38/p38 ratios, GlcN induced the KLF4 (Krüppel-like factor 4) and SIRT1 (Sirtuin-1) proteins. Furthermore, GlcN mitigated hyperglycemic-induced reactive oxygen species (ROS) and cellular senescence, and elevated the population of cells in the subG1 and S phases but reduced the population in the G1 phase. Hyperglycemia-induced KLF4 proteins and SIRT1 and fibronectin proteins were enhanced and suppressed by 10 mM GlcN, respectively. GlcN induced the expression of the tight junction protein claudin-1, which was otherwise suppressed in hyperglycemic conditions. Lastly, two SIRT1 inhibitors Ex-527 and INZ mitigated GlcN-induced claudin-1 expression and suppression of hyperglycemic-induced ROS generation. Our study may provide valuable insights into developing therapeutic strategies that utilize GlcN to rejuvenate the corneal epithelium in patients experiencing oxidative and senescent stresses due to poor glycemic control.