GTF2H4 regulates partial EndMT via NF-κB activation through NCOA3 phosphorylation in ischemic diseases

Partial endothelial-to-mesenchymal transition(EndMT)is an intermediate phenotype observed in endothelial cells(ECs)undergoing a transition toward a mesenchymal state to support neovascularization during(patho)physiological angiogenesis.Here,we investigated the occurrence of partial EndMT in ECs under hypoxic/ischemic conditions and identified general transcription factor IIH subunit 4(GTF2H4)as a positive regulator of this process.In addition,we discovered that GTF2H4 collaborates with its target protein excision repair cross-complementation group 3(ERCC3)to co-regulate partial EndMT.Furthermore,by using phosphorylation proteomics and site-directed mutagenesis,we demonstrated that GTF2H4 was involved in the phosphorylation of receptor coactivator 3(NCOA3)at serine 1330,which promoted the interaction between NCOA3 and p65,resulting in the transcriptional activation of NF-κB and the NF-kB/Snail signaling axis during partial EndMT.In vivo experiments confirmed that GTF2H4 significantly promoted partial EndMT and angiogenesis after ischemic injury.Collectively,our findings reveal that targeting GTF2H4 is promising for tissue repair and offers potential opportunities for treating hypoxic/ischemic diseases.

miR-130b inhibits proliferation and promotes differentiation in myocytes via targeting Sp1

Muscle regeneration after damage or during myopathies requires a fine cooperation between myoblast proliferation and myogenic differentiation.A growing body of evidence suggests that microRNAs play critical roles in myocyte proliferation and differentiation transcriptionally.However,the molecular mechanisms underlying the orchestration are not fully understood.Here,we showed that miR-130b is able to repress myoblast proliferation and promote myogenic differentiation via targeting Sp1 transcription factor.Importantly,overexpression of miR-130b is capable of improving the recovery of damaged muscle in a freeze injury model.Moreover,miR-130b expression is declined in the muscle of muscular dystrophy patients.Thus,these results indicated that miR-130b may play a role in skeletal muscle regeneration and myopathy progression.Together,our findings suggest that the miR-130b/Sp1 axis may serve as a potential therapeutic target for the treatment of patients with muscle damage or severe myopathies.

Nanotechnology for cardiovascular diseases

Cardiovascular diseases have become the major killers in today’s world,among which coronary artery diseases(CADs)make the greatest contributions to morbidity and mortality.Although state-of-the-art technologies have increased our knowledge of the cardiovascular system,the current diagnosis and treatment modalities for CADs still have limitations.As an emerging cross-disciplinary approach.