Diabetes mellitus refers to several metabolic disorders, all characterized by chronic hyperglycemia. In this disease, the ability to produce the hormone insulin is lost (type 1), or the body's cells become resistant to insulin (type 2). When blood sugar levels increase and affect metabolism, complications of the disease become noticeable [1, 2]. Cardiovascular, kidney and eye complications, problems of the nervous system, disorders of peripheral organs due to nerve damage and finally, heart and ischemic stroke are complications of diabetes in the body . Diabetes is the seventh most common disease in the world in terms of economic and social burden. According to the World Health Organization, more than 488 million people were diagnosed with diabetes in 2014, and more than 1.6 million deaths were directly attributable to diabetes in 2016 .
Lung tissue is highly prone to damage and microvascular complications in diabetes because of its large vascular extent and abundant connective tissue . Decreased lung function in people with diabetes is directly related to blood glucose levels, duration of diabetes, and severity of nonsmoking disease and obesity .
High blood glucose levels and the duration of the disease also increase the clinical symptoms of chronic lung disease . Changes in the lung tissue of patients with diabetes include 1) an increase in the thickness of the basement membrane, which is due to an inflammatory process in the lungs of a patient with diabetes. 2) neutrophil infiltration and accumulation, and an increase in alveolar wall thickness, and 3) fibrosis toward inflammatory cell infiltration, as seen in hematoxylin and eosin staining [8, 9]. The effects of diabetes on the lungs and pulmonary disease have been demonstrated in many clinical studies. However, the pathophysiology and mechanism of the effects of diabetes on pulmonary problems are still largely unknown and unclear. Previous studies have shown pathologic changes in the lung tissue of patients with diabetes, but the exact mechanism of these changes is unknown [6, 8, 10].
MicroRNAs (miRNA) are small, uncoded, protected RNAs 18–25 nucleotides in length that control gene expression after transcription by inhibiting translation or initiating degradation of mRNAs . It has also been shown that each miRNA has hundreds of target genes. Thus, even if the expression of a miRNA is changed, it has a significant impact on regulating target genes . Their expression may be a marker of tissue health or disease. These miRNAs can be used as potential biomarkers for diagnosis, and prognosis .
To date, the involvement of many miRNAs in diabetic complications such as retinopathy, nephropathy, neuropathy, and cardiovascular and pulmonary complications has been demonstrated [12, 14]. Also decrease the expression of miRNA-155 in severe asthma and its inhibition in people with lung inflammation and ductal mucus secretion. MiRNA-15 decreases the number and secretion of Th2 lymphocytes . In asthma, the level of miRNA-133a decreases . In asthmatic mice models increasing the expression of this miRNA decreases airway remodeling (by affecting airway smooth muscle) . miRNA-133a expression is decreased in the bronchial smooth muscle of asthma patients, which increases RhoA levels and improves bronchial response and sensitivity . MiR133a has a protective effect against fibrosis in human lung fibroblasts (HFL). It suppresses myofibroblast development and progression of pulmonary fibrosis by inhibiting TGF-1 . It is noteworthy that quantitative proteomics research has shown that miRNA-133a suppresses myofibroblast development by targeting numerous components of the profibrogenic TGF-1 pathway. Western blot studies showed that miR-133a suppressed the production of traditional myofibroblast differentiation markers such as -smooth muscle actin (SMA), connective tissue growth factor (CTGF), and collagens in response to TGF-1 stimulation .
The level of miRNA-155 in the serum of patients with type 2 diabetes is low , suggesting that miRNA-155 controls blood glucose levels in patients with diabetes. Genetically modified mice expressing higher levels of miRNA-155 were more to have hypoglycemia and increased insulin sensitivity [21, 22]. The level of miRNA-155 in foot ulcers of study participants in the diabetes group is higher than usual , which suppresses FGF7, effective in wound healing and wound epithelialization. By inhibiting miRNA-155, the wound healing rate was significant . Studies on the inhibition of miRNA in preclinical models of asthma, cystic fibrosis (CF), and IPF have shown that therapeutic targets are satisfactory [23–25]. In animals, microRNA inhibitors administered directly into the respiratory tract via nebulizers or inhalers increase the expression of groups of genes with complementary "seed" sequences in their mRNA-untranslated regions for selective and targeted microRNA binding. These results show that it is possible to change the way microRNAs work to develop new treatments for chronic lung diseases .
Glycosylated protein in the lung and thoracic tissues after hyperglycemia, the resistance of collagen to proteolysis, and finally, the accumulation of this protein in lung connective tissue may cause lung disease in patients with diabetes. Understanding the mechanism of these disorders will help diagnose and treat the lung damage caused by diabetes. MiRNAs are markers for various diseases. Therefore, in this study, we investigated the effects of type 2 diabetes on lung tissue damage and the expression of miRNA-155 and miRNA-133a in lung tissue of male rats.