ABSTRACT
Type 2 diabetes mellitus (T2DM) is a metabolic disease with an increasing incidence worldwide, which leads to damage to various tissues and organs including the liver. MiR-31 is conserved across species and closely associated with metabolic diseases, but its role in type 2 diabetic liver injury has not been elucidated. This study aimed to investigate the effect of miR-31 on liver injury in type 2 diabetes and its underlying mechanism. Four to six weeks old male FVB mice and miR-31-positive transgenic mice were randomly divided into FVB mice control group (C), FVB mice induced diabetes group (DM) and miR-31-overexpression transgenic mice induced diabetes group (31DM). After 1 week of adaptive feeding, the T2DM mouse model was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ) for 6 weeks. The general condition of mice and related metabolic indicators showed that the increased food and water intake, weight loss and glucose and lipid metabolism disorders could be reversed by miR-31 in T2DM mice. HE staining and liver histological activity index (HAI) scoring results showed that miR-31 improved the inflammatory status in the liver tissue of T2DM mice and decreased the HAI score. RT-qPCR results showed that the high expression of miR-31 was accompanied by a decrease in the expression of activating transcription factor 6 (ATF6) mRNA in the liver of T2DM mice. Furthermore, Western blotting results showed that miR-31 inhibited the expression of endoplasmic reticulum stress-related proteins such as ATF6, glucoregulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the liver of T2DM mice. In conclusion, miR-31 may ameliorate liver injury in T2DM mice by regulating glucose and lipid metabolism disorders and insulin resistance, and inhibiting endoplasmic reticulum stress factors such as ATF6, GRP78, and CHOP.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the significance of intercellular adhesion molecule -1 (CD54 or ICAM-1), epidermal growth factor receptor (EGFR) and platelet-derived factor (PDGF) in sputum cells of workers exposed to dust and patients with pneumoconiosis for the early diagnosis of pneumoconiosis.</p><p><b>METHODS</b>The subjects included 62 workers exposed to dusts, 51 workers not exposed to dusts, 22 patients with pneumoconiosis and 10 healthy controls. The respiratory sputum technique was used to collect the sputum samples and the biomarkers (ICAM-1, EGFR and PDGF) of the sputum samples were detected with the sputum samples.</p><p><b>RESULTS</b>When the exposure group was compared with non-exposure group, there were no significant differences of surface biomarkers (ICAM-1, EGFR and PDGF) in sputum cells (neutrophil leucocytes, macrophages, lymphocytes and acidophilic/basophil leucocytes). As compared with other workers exposed to dusts, the surface CD54 and EGFR expression levels increased significantly and the surface PDGF expression level decreased significantly in workers exposed to dusts for 10 years (P<0.05). As compared with controls, the CD54 and EGFR expression levels of sputum cells increased significantly and the PDGF expression level of sputum cells decreased significantly in patients with pneumoconiosis at the stages of I and II + mI (P<0.05).</p><p><b>CONCLUSION</b>The expression levels of the surface CD54, EGFR and PDGF of sputum cells in workers exposed to dusts and patients with pneumoconiosis changed, which may be useful for early detecting pneumoconiosis.and patients is changed, which may be meaningful for early detection of pneumoconiosis.</p>