Endothelial cells control muscle regeneration through angiocrine lactate

We studied metabolic angiocrine mechanisms by which endothelial cell_ECs_ can contribute to muscle regeneration from ischemia by using endothelial specific pfkfb3 knockout mice_pfkfb3DEC_ after hind-limb ischemia_HLI_. During muscle regeneration, monocytes are recruited to the injured area and rapidly become macrophages which initially exhibit a more pro-inflammatory M1-like phenotype but soon thereafter functionally repolarize towards an M2-like phenotype to actively support muscle regeneration. Interestingly, macrophages derived from pfkfb3DEC failed to polarized to M2-like macrophages after HLI. Reduced macrophage polarization impairs angiogenesis and muscle regeneration. The RNAseq data are pfkfb3DEC and pfkfb3WT muscle derived macrophages 3 days after HLI. Overall design: pfkfb3?EC and pfkfb3WT muscle derived macrophages 3 days after HLI.

本研究通过构建后肢缺血（hind-limb ischemia, HLI）模型，利用内皮细胞（endothelial cell, EC）特异性pfkfb3敲除小鼠（pfkfb3DEC），探究内皮细胞通过代谢性血管分泌机制调控缺血后肌肉再生的潜在机制。在肌肉再生过程中，单核细胞被招募至损伤区域并快速分化为巨噬细胞：此类巨噬细胞初始呈现促炎型M1样表型，随后迅速发生功能极化为M2样表型，以主动支持肌肉再生。值得注意的是，HLI模型术后，源自pfkfb3DEC小鼠的巨噬细胞无法极化为M2样巨噬细胞。巨噬细胞极化缺陷会损害血管生成与肌肉再生过程。本研究的RNA测序（RNAseq）数据来源于HLI模型术后3天的、pfkfb3DEC与pfkfb3WT小鼠的肌肉来源巨噬细胞。实验整体设计：HLI模型术后3天的pfkfb3DEC与pfkfb3WT小鼠肌肉来源巨噬细胞。