MicroRNAs (miRNAs) are a class of small non-coding RNAs of 20–25 nucleotides in length. It has been shown that miRNAs play important roles in the proliferation of many types of cells, including myoblasts. In this study, we used real-time quantitative polymerase chain reaction, western blotting, EdU, flow cytometry, and CCK-8 assay to explore the role of miR-125a-5p during the proliferation of C2C12 myoblasts. It was found that the expression of miR-125a-5p was decreased during C2C12 myoblast proliferation. Over-expression of miR-125a-5p inhibited C2C12 myoblast proliferation as indicated by EdU staining, flow cytometry, and CCK8 assay. It was also found that miR-125a-5p could negatively regulate E2F3 expression at posttranscriptional level, via a specific target site in the 3′ untranslated region. Knockdown of E2F3 showed a similar inhibitory effect on C2C12 myoblast proliferation. Thus, our findings suggest that miR-125a-5p may act as a negative regulator of C2C12 myoblast proliferation by targeting E2F3.

The present study is aimed at investigating the molecular mechanism of C1q/TNF-related protein 9 (CTRP9) and providing a new perspective in arteriovenous shunt-induced pulmonary arterial hypertension (PAH). PAH was established by an arteriovenous shunt placement performed in rats. Adenovirus(Ad)-CTRP9 and Ad-green fluorescent protein viral particles were injected into the rats through the tail vein. Following 12 weeks, the mean pulmonary arterial pressure (mPAP) and right ventricular systolic pressure (RVSP) were measured and morphological analysis was conducted to confirm the establishment of the PAH model. The systemic elevation of CTRP9 maintained pulmonary vascular homeostasis and protected the rats from dysfunctional and abnormal remodeling. CTRP9 attenuated the pulmonary vascular remodeling in the shunt group by decreasing the mPAP and RVSP, which was associated with suppressed inflammation, apoptosis, and extracellular matrix injury. In addition, CTRP9 dramatically increased the phosphorylation of AKT and p38-MAPK in the lung tissues of shunt-operated animals. These findings suggest a previously unrecognized effect of CTRP9 in pulmonary vascular homeostasis during PAH pathogenesis.

Atherosclerosis constitutes a pathological process underlying cardiovascular diseases. There is growing evidence that IGFBP5 is a causative factor, although the conclusions of different studies are inconsistent. The present study aims to confirm the role and mechanism of IGFBP5 in atherosclerosis. The expression of IGFBP5 was induced in the skeletal muscle of male ApoE^−/− mice, an atherosclerosis model, using adeno-associated virus, resulting in elevated circulating IGFBP5 levels. Changes in blood lipids were detected, and pathological changes in the aorta were observed. Analysis of IGFBP5 function using RNA sequencing and validation were performed in a mouse aortic smooth muscle cell line. The results demonstrated that IGFBP5 overexpression exacerbated the development of aortic lesions in this murine models without any discernible alterations in lipid profile parameters; the arterial transcriptomic landscape revealed that heightened IGFBP5 levels predominantly influenced pathways governing smooth muscle cell proliferation and motility. In vitro experimentation corroborated these findings, showcasing the stimulatory effect of IGFBP5 on VSMC (vascular smooth muscle cell) proliferation and migration, provoking a transition toward a proliferative phenotype. IGFBP5 promotes atherosclerosis in ApoE^−/− mice through the phenotypic transformation of VSMCs. This finding suggests that IGFBP5 has the potential to serve as an indicator of atherosclerosis diagnosis and a target for therapeutic interventions in the future.

Glucocorticoid‐induced osteoporosis (GIO) is driven by a pathogenic shift in bone marrow mesenchymal stem cell (BMSC) lineage commitment from osteogenesis to adipogenesis. Here, we identify Microtubule Actin Cross‐linking Factor 1 (MACF1) as a critical regulator of MSC fate that is severely suppressed during long‐term glucocorticoid (GC) exposure. We demonstrate that MACF1 deficiency phenocopies GC‐induced marrow adiposity and bone loss. Crucially, restoring endogenous MACF1 via promoter‐targeted small activating RNA (saRNA) effectively corrects this fate bias and reverses microarchitectural deterioration in GIO mice. Mechanistically, MACF1 acts as a key facilitator of vesicular trafficking. By orchestrating the assembly of the Rab14/KIF16B complex, MACF1 drives the precise anterograde transport of Fibroblast Growth Factor Receptors (FGFRs) to the plasma membrane. GC exposure downregulates MACF1, disrupting this transport machinery and causing intracellular FGFR sequestration. This transport failure depletes functional cell‐surface FGFRs, thereby blunting osteogenic signaling and triggering the adipogenic shift. Collectively, our findings establish the MACF1‐governed intracellular trafficking network as an important determinant of FGFR spatial distribution and MSC fate, highlighting it as a promising therapeutic target for restoring bone‐fat equilibrium in GIO.