《HDAC6 inhibitor accelerates wound healing by inhibiting tubulin mediated IL-1β secretion in diabetic mice》 was written by Karnam, Kalyani; Sedmaki, Kavitha; Sharma, Pravesh; Routholla, Ganesh; Goli, Sriharshini; Ghosh, Balaram; Venuganti, Venkata Vamsi Krishna; Kulkarni, Onkar Prakash. Related Products of 1445-73-4 And the article was included in Biochimica et Biophysica Acta, Molecular Basis of Disease in 2020. The article conveys some information:
Delayed wound healing in diabetes is characterized by sustained activation of inflammasome and increased expression of IL-1β in macrophages. Identification and validation of novel pathways to regulate IL-1β expression will provide therapeutic targets for diabetic wounds. Here we report sustained over-expression of histone deacetylase 6 (HDAC6) in wounds of diabetic mice and its role in delayed wound healing. Topical application of HDAC6 inhibitor; Tubastatin A (TSA) gel promoted the wound healing in diabetic mice. TSA hydrogel reduced the infiltration of neutrophils, T-cells and macrophages in the early phase of wound healing. TSA treatment promoted the wound healing by inducing collagen deposition, angiogenesis (CD31) and fibrotic factors (TGF-β1) in the late phase of healing. Protein anal. of the diabetic wounds treated with TSA showed increased acetylated α-tubulin and decreased levels of mature IL-1β with no significant effect on the expression of pro-IL-1β, pro-caspase-1 and active caspase-1. In in vitro assays, macrophages exhibited upregulation of HDAC6, IL-1β and downregulation of IL-10 upon stimulation with high glucose and LPS. TSA inhibited the IL-1β secretion and promoted IL-10 in stimulated macrophages with high glucose and LPS. Further investigations showed that TSA inhibits IL-1β release by inhibiting tubulin dependent lysosomal exocytosis without affecting its transcription and maturation. Nocodazole (known acetylation inhibitor) pre-treatment inhibited TSA effect on IL-1β secretion in high glucose stimulated macrophages. Overall, our findings indicate that sustained HDAC6 expression in diabetic wounds contributes to impaired healing responses and HDAC6 may represent a new therapeutic target for diabetic wounds. In the experimental materials used by the author, we found 1-Methyl-4-piperidone(cas: 1445-73-4Related Products of 1445-73-4)
1-Methyl-4-piperidone(cas: 1445-73-4) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.Related Products of 1445-73-4
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem