RESUMO
The morbidity and mortality of cardiovascular disease (CVD) are relatively high. Studies have shown that most patients with chronic kidney disease (CKD) die from cardiovascular complications. Clinically, the pathophysiological state in which heart disease and kidney disease are causal and influence each other is called cardiorenal syndrome (CRS). Myocardial hypertrophy is the key stage of the heart structure changing from reversible to irreversible. It is an important pathophysiological basis for heart failure. Therefore, this study intends to start with the end-stage uremic phase of CKD to construct an animal model of uremia in rats to study the relationship between uremia, TLR4/MyD88 signaling pathway, and myocardial hypertrophy. The results showed that the uremic rats showed slow weight gain and were thinner. At 12 weeks (w), the serum creatinine and urea nitrogen of the uremic rats increased, and the global hypertrophy index increased. Detecting the expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor (MyD88) in blood samples of rats, we found that the expression of TLR4 and MyD88 increased at 12 w in the uremia group; pathological observation showed that at 4 weeks of uremia model rats, renal tissue compensatory hypertrophy, renal fibrous membrane proliferation, renal parenchyma atrophy, a large number of fibrous proliferation and inflammatory cell infiltration in the interstitium, and protein casts in the renal tubules were observed. Myocardial cells were obviously hypertrophy and disordered. At 12 w, renal tubules were obviously expanded, the epithelium was flat, the brush border disappeared, and the interstitial fibrous connective tissue of the myocardial tissue was proliferated. The detection of TLR4 and MyD88 in kidney tissue and myocardial tissue revealed that the positive expression of TLR4 and MyD88 gradually increased over time. Therefore, the final result of the study is that uremia can gradually lead to myocardial hypertrophy and TLR4 and MyD88 are highly expressed in serum, kidney, and myocardial tissues of uremic rats, suggesting that TLR4 and MyD88 may be related to the degree of uremic disease and the myocardium caused by it. Hypertrophy is related.
RESUMO
Alternative splicing (AS) is a complex coordinated transcriptional regulatory mechanism. It affects nearly 95% of all protein-coding genes and occurs in nearly all human organs. Aberrant alternative splicing can lead to various neurological diseases and cancers and is responsible for aging, infection, inflammation, immune and metabolic disorders, and so on. Though aberrant alternative splicing events and their regulatory mechanisms are widely recognized, the association between autoimmune disease and alternative splicing has not been extensively examined. Autoimmune diseases are characterized by the loss of tolerance of the immune system towards self-antigens and organ-specific or systemic inflammation and subsequent tissue damage. In the present review, we summarized the most recent reports on splicing events that occur in the immunopathogenesis of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and attempted to clarify the role that splicing events play in regulating autoimmune disease progression. We also identified the changes that occur in splicing factor expression. The foregoing information might improve our understanding of autoimmune diseases and help develop new diagnostic and therapeutic tools for them.