The Reduced Expression of EOLA1 May Be Related to Refractory Diabetic Foot Ulcer

Abstract

Background. Chronic diabetic foot ulcer (DFU) is one of the most intractable complications of diabetes mellitus (DM). Its pathogenesis is complex, and uncontrolled chronic inflammation is an important factor. Endothelial overexpressed lipopolysaccharide-associated factor 1 (EOLA1) discovered in our laboratory is an intracellular protein with the function of inflammatory regulation. This study was aimed at observing the expression of EOLA1 in DFU skin tissues and its relationship with inflammation and at exploring the possible role of EOLA1 in DFU and its mechanism. Methods. The patients with DFU were divided into 2 groups based on the formation time of ulcer: the acute wound (AW) group with the course of disease≤4 weeks and the chronic wound (CW) group with the course of disease>4 weeks. The relevant clinical data of patients were collected, and the skin tissues around the ulcer were used for immunofluorescence detection and immunohistochemical staining to observe inflammation. The expression levels of EOLA1, metallothionein 2A (MT2A), nuclear factor-κB (NF-κB), and interleukin-6 (IL-6) were detected by western blot. Results. A total of 79 patients were enrolled in the study. The results of immunofluorescence and immunohistochemistry showed that EOLA1 was expressed in the epithelial tissues of DFU. However, the expression of EOLA1 in the CW group was significantly lower than that in the AW group (P<0.05), and the expression of NF-κB and IL-6 was obviously increased (P<0.05). Conclusion. The refractory wounds in patients with DFU may be closely related to the uncontrolled activation of inflammatory pathways in cells caused by the reduced expression of negative regulators of inflammation (e.g., EOLA1), and such decreased expression may be also strongly linked to the persistent state of inflammation.

Downregulation of metallothionein-2 contributes to oxaliplatin-induced neuropathic pain

“…Consistent with our findings with MT2 restoration, we found that genetic inhibition of MT2 by intrathecal injection of MT2A siRNA in turn induced mechanical allodynia in normal mice through a similar neuroinflammatory signaling pathway. Our data are in line with previous reports showing a significant relationship between MT2 expression and cell inflammatory responses that act by suppressing NF-κB signaling activation [ 32 , 36 ]. Therefore, MT2 is likely to contribute to oxaliplatin-induced neuropathic pain through the inactivation of the NF-κB signaling pathway in the spinal dorsal horn.…”

Downregulation of Metallothionein-2 Contributes to Oxaliplatin-induced Neuropathic Pain

“…Consistent with our ndings with MT2 restoration, we found that genetic inhibition of MT2 by intrathecal injection of MT2A siRNA in turn induced mechanical allodynia in normal mice through a similar neuroin ammatory signaling pathway. Our data are in line with previous reports showing that a signi cant relationship between MT2 expression and cell in ammatory responses that acts by suppressing NF-κB signaling activation [32,36]. Therefore, MT2 is likely to contribute to oxaliplatin-induced neuropathic pain through inactivation of the NF-κB signaling pathway in the spinal dorsal horn.…”

IL-1B can serve as a healing process and is a critical regulator of diabetic foot ulcer

“…Aside from the main etiological factors, several factors also have critical roles in the occurrence and processes of DFU, including abnormal gene alterations, immune cell infiltration, and inflammation (4)(5)(6). Wu et al found that the downregulation of endothelium and lymphocyte associated ASCH domain 1 (EOLA1) expression exacerbated DFU by enhancing the inflammatory pathway activity, and also detected differentially expressed genes (DEGs), including metallothionein 2A and interleukin (IL)-6 (6).…”