Analyses of Long Noncoding RNA and mRNA Profiles in Subjects with the Phlegm-Dampness Constitution

Abstract

Background. Constitution in traditional Chinese medicine (TCM) plays a key role in the genesis, development, and prognosis of diseases. Phlegm-dampness constitution (PDC) is one of the nine constitutions in TCM, susceptible to metabolic disorders, which is mainly manifested by profuse phlegm, loose abdomen, and greasy face. Epidemiologic, genomic, and epigenetic studies have been carried out in previous works, confirming that PDC represents a distinctive population with microcosmic changes related to metabolic disorders. However, whether long noncoding RNAs (lncRNAs) play a regulatory role in metabolic disease in subjects with PDC remains largely unknown. We aimed to investigate distinct lncRNA and mRNA expression signatures and lncRNA-mRNA regulatory networks in the phlegm-dampness constitution (PDC). Methods. The peripheral blood mononuclear cells (PBMCs) were isolated from the subjects with PDC ( n = 13 ) and balanced constitution (BC) ( n = 9 ). The profiles of lncRNAs and mRNAs in PBMCs were analyzed using microarray and further validated with RT-qPCR. Subsequently, pathway analysis was performed to investigate the function of differentially expressed mRNAs by using Ingenuity Pathway Analysis (IPA). Results. Results suggested that some mRNAs, which were regulated by the differentially expressed lncRNAs, were mainly enriched in lipid metabolism and immune inflammation-related pathways. This was consistent with the molecular characteristics of previous studies, indicating that the clinical characteristics of metabolic disorders in PDC might be regulated by lncRNAs. Furthermore, by making coexpression network construction as well as cis-regulated target gene analysis, several lncRNA-mRNA pairs with potential regulatory relationships were identified by bioinformatic analyses, including RP11-317J10.2-CA3, RP11-809C18.3-PIP4K2A, LINC0069-RFTN1, TTTY15-ARHGEF9, and AC135048.13-ORAI3. Conclusions. This study first revealed that the expression characteristics of lncRNAs/mRNAs may be potential biomarkers, indicating that the distinctive physical and clinical characteristics of PDC might be partially attributed to the specific expression signatures of lncRNAs/mRNAs.

Association between the traditional Chinese medicine constitution and metabolic dysfunction-associated fatty liver disease in older people: A cross-sectional study

“…This finding indicates a potential risk of metabolic disorders in individuals with the PDC [ 37 ]. In recent years, studies on molecular mechanisms (e.g., DNA methylation, RNA, intestinal flora) have demonstrated, in several aspects, that PDC formation is associated with insulin resistance, oxidative stress, increase in free fatty acids, energy metabolism, endocrine disorders, genetics, and disorders in the metabolism of glucose and lipids [ [38] , [39] , [40] ]. In conclusion, the PDC is closely related to the occurrence and development of MAFLD.…”

“…A healthy lifestyle is essential to counteract the early stages of MAFLD [ 49 ]. The TCMC is also an important basis for predicting the progression, regression, and prognosis of a disease [ 38 ]. Also, study of the PDC is a good entry point to explore metabolic disorders [ 42 , 50 ].…”

“…The disease spectrum of the PDC is dominated by metabolic disorders, as well as cardiovascular and cerebrovascular diseases [ 51 ]. Regardless of the disease, people with the PDC carry a higher risk of metabolic disorders [ 38 ]. Therefore, combining the TCMC with disease susceptibility, identifying susceptible people, and improving the TCMC can prevent diseases before they occur, prevent them from spreading, and aid interventions.…”

Discussion on prevention and treatment of ischemic stroke from the phlegm-dampness constitution

“…Endothelial dysfunction is involved throughout the development of atherosclerosis and is a key link in its formation [17]. Studies have shown that sputum-dampness constitution presents the propensity of both insulin resistance, lipid metabolism as well as disorders of purine metabolism in the undiagnosed state [18], and considered that they are risk factors for the formation of atherosclerosis caused by vascular endothelial dysfunction induced by phlegm-dampness constitution .For example, patients with sputum-dampness constitution have decreased serum levels of HDL-C and increased levels of TC, TG, and LDL-C [19]. The elevation of blood lipids and cholesterol can directly induce endothelial cells to undergo oxidative stress and inflammatory reactions, resulting in endothelial dysfunction [20]; While insulin resistance can induce NOx activation to produce a large amount of oxygen free radicals and inhibit the activation of eNOS [21], thus aggravating endothelial function injury and accelerating the formation of atherosclerosis.…”

DIA-PRM Proteomic Analysis of Phlegm-Dampness Constitution with Glucolipid Metabolic Disorders by the Intervention of Hua Tan Qu Shi Recipe

“…Epidemiologic studies have reported that phlegm-dampness constitution is highly related to diabetes and metabolic syndromes (MS) [9]. Genomic studies have illustrated that phlegm-dampness constitution has the molecular basis of metabolic disorder and is the potential risk for arteriosclerosis and thrombosis; the individuals are susceptible to hyperlipemia and diabetes [10], and various genes in the phlegm-dampness constitution are involved in glucose and lipid metabolism pathways [11]. In addition, single-nucleotide polymorphisms and methylation investigation have also confirmed that phlegm-dampness constitution is closely related to GLMD [12].…”