Low temperature induces cryoinjury in mouse corneal endothelial cells by stimulating the Stk11-p53 signal pathway

Abstract

Cryoinjury, or injury caused by extremely low temperatures, can occur in corneal endothelial cells (CECs) and lead to visual impairment. However, the mechanism of cryoinjury in CECs is not clear. The Stk11-p53 signaling pathway regulates the proliferation and division of cells. Activity of the Stk11-p53 signaling pathway arrests the cell cycle at the G0/G1 phase and induces apoptosis. In this study, a mouse model of cryoinjury in CECs was used. Following injury, significant mouse CEC death and shedding were observed. In addition, the mRNA and protein levels of core factors from the Stk11-p53 signaling pathway (Stk11, p21 and p53) were elevated and Caspase-3 was activated following cryoinjury. In addition, chromatin immunoprecipitation revealed that Stk11 catalyzed p53 serine 15 phosphorylation, and the Stk11-p53 complex bound to the p21 promoter and stimulated gene transcription. Thus, the results of the present study suggest that cryoinjury leads to the damage and apoptosis of mouse CECs by activation of the Stk11-p53 signaling pathway, phosphorylation of p53 serine 15 and p21 gene transcription.

Amniotic fluid mesenchymal stem cells repair mouse corneal cold injury by promoting mRNA N4-acetylcytidine modification and ETV4/JUN/CCND2 signal axis activation

“…The cornea is divided into five layers, which are listed from posterior to anterior as follows: Epithelium, lamina elastica anterior (Bowman membrane), stroma, lamina elastica posterior (Descemet membrane), and endothelium [1][2][3][4][5][6].…”

“…CECs line the posterior surface of the cornea and face the anterior chamber. They also regulate the passage of fluids and solutes across the posterior surface of the cornea to maintain a slightly dehydrated state, which is required for transparency and refraction [1][2][3][4][5][6]. CECs are critical to maintain the structure and function of the cornea; they also possess a barrier function, regulate osmotic pressure, and control the active transport of fluid out of the cornea via the activity of the Na + /K + -ATPase to maintain normal corneal metabolism [1][2][3][4][5].…”

“…The cornea is divided into five layers, which are listed from posterior to anterior as follows: Epithelium, lamina elastica anterior (Bowman membrane), stroma, lamina elastica posterior (Descemet membrane), and endothelium [ 1 – 6 ]. The endothelium is arranged as a single layer of hexagonal smooth corneal endothelial cells (CECs).…”

“…Corneal damage might be caused by a number of factors, including mechanical injury, exposure to solar radiation over an extended period of time, exposure to chemicals, and freezing [ 7 , 8 ]. Corneal injury caused by freezing of CECs is common in the cold areas of the world and can damage vision [ 6 ]. Severe corneal injury leads to permanent corneal swelling and bullous keratopathy, and is considered one of the main causes of loss of visual function.…”

“…Severe corneal injury leads to permanent corneal swelling and bullous keratopathy, and is considered one of the main causes of loss of visual function. Although corneal transplantation is a good method to treat corneal injury, the application and development of this treatment method is limited for various reasons, especially a lack of corneal donors [ 6 ]. Therefore, it is difficult to repair and treat corneal injury caused by freezing.…”