8/23/2023 0 Comments Tao jun kun dodemonstrated that lncRNA H19/miR-675/PTEN was the signaling axis in SMC proliferation. Competing endogenous RNAs (ceRNAs) are stable lncRNAs that accumulate in large numbers and modulate gene expression in different ways, including decoys or sponges for miRNAs. They can regulate gene expression post-transcriptionally by base-pairing with mRNAs to modulate their translation and/or stability. Long noncoding RNAs (lncRNAs), a class of noncoding RNAs longer than 200 nt in length, are actively regulated during cellular senescence. However, the role of BMF in regulating VSMC calcification/senescence still needs to be further explored. In addition, BMF could also promote VSMC apoptosis by regulating miR-221/222 expression. confirmed that BMF could promote apoptosis of proximal renal tubular cells in mice with diabetic nephropathy. found that miR-34c could increase the expression of Bcl-2 and inhibit the apoptosis of renal podocytes in a high glucose environment. Bcl-2 modifying factor (BMF) has been reported to play an important role in the regulation of cell functions under hyperglycemia. It is well known that miRNAs exerted their functions by regulating translation or stability of target mRNAs. However, the detailed mechanism of the function of miR-34c in VSMC calcification/ senescence is not yet fully understood. MiR-34c, a member of miR-34 family, is reported to participate in osteoblast differentiation, VSMC calcification, endothelial senescence, and many others. Presently, miRNAs have been verified to control gene expression by binding to 3’ untranslated regions (UTR) of target genes, and the impacts of miRNAs on regulating the proliferation, migration, differentiation, calcification, and apoptosis of VSMCs have been investigated in numerous fields. MicroRNAs (miRNAs) are a class of small noncoding RNAs with the length of ~22 nt. Moreover, the mechanisms involved in high glucose-induced VSMC calcification/senescence remain unclear. However, very few reports have studied the effect of high glucose on calcification/senescence of vascular smooth muscle cells (VSMCs). Hyperglycemia is the main characteristic of diabetes and increasing evidence has demonstrated that high glucose is an important regulator of endothelial cell senescence, wherein accumulative premature senescent cells participate in the onset and progress of diabetic vascular aging. Furthermore, diabetic artery calcification/aging leads to arteriosclerosis, amputations, kidney failure, stroke, and increased incidence of cardiovascular events and mortality. Vascular calcification is an important phenotype of vascular aging and is one of the common effects of macrovascular complications in patients with diabetes, mainly involving the media of artery, also termed Monckeberg’s arterial calcification. Vascular aging is very common in patients with diabetes and it can influence the threshold, progression, severity, and prognosis of the cardiovascular disease. Our results showed for the first time that the calcification/senescence of VSMCs was regulated by lncRNA-ES3 /miR-34c-5p/BMF axis. Further, lncRNA-ES3 inhibited miR-34c-5p expression by direct interaction and its knockdown suppressed the calcification/senescence of HA-VSMCs. Besides, lncRNA-ES3 acted as a competing endogenous RNAs (ceRNA) of miR-34c-5p to enhance BMF expression. Bcl-2 modifying factor (BMF) was a functional target of miR-34c-5p and it was involved in the process of calcification/senescence of HA-VSMCs. Overexpression of miR-34c-5p alleviated calcification/senescence of HA-VSMCs, whereas inhibition of miR-34c-5p received the opposite results. MiR-34c-5p, not miR-34c-3p, was suppressed significantly in calcification/senescence of human aorta vascular smooth muscle cells (HA-VSMCs) induced by high glucose, which was proven by the formation of mineralized nodules and staining of senescence associated-β-galactosidase staining (SA β-gal) positive cells. Vascular calcification/aging is common in diabetes and is associated with increased morbidity and mortality of patients.
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