Muscle progenitor cells are required for skeletal muscle regeneration and prevention of adipogenesis after limb ischemia.
Muscle progenitor cells are required for skeletal muscle regeneration and prevention of adipogenesis after limb ischemia.
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DOI：
10.3389/fcvm.2023.1118738
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发表时间：
2023
影响因子：
3.6
通讯作者：
Kontos, Christopher D.
中科院分区：
文献类型：
--
作者：
Abbas, Hasan;Olivere, Lindsey A.;Padgett, Michael E.;Schmidt, Cameron A.;Gilmore, Brian F.;McCord, Timothy J.;Southerland, Kevin W.;McClung, Joseph M.;Kontos, Christopher D.
关键词：
外周动脉疾病(PAD)的骨骼肌损伤被认为是血管功能不全所致，然而有证据表明，肌肉细胞的反应在决定肢体缺血的预后中起着重要作用。在这里，我们证明，在后肢缺血(HLI)模型中，Pax7+肌祖细胞(MPC)的遗传消融抑制了缺血损伤后的肌肉再生，尽管静息肌肉缺乏形态或生理变化。与对照小鼠(Pax7wt)相比，Pax7缺陷小鼠的缺血肢体(Pax7Δ)在HLI后7天或28 不能产生显著的力量。HLI后28 ，Pax7Δ小鼠缺血肢体脂肪显著增加，取代了功能性肌肉。在Pax7Δ小鼠中，脂肪生成与PDGFRα+纤维/成脂前体细胞(FAP)的显着增加相对应。使用巴替马斯特抑制FAPs可减少肌肉脂肪，但增加纤维化。在体外，Pax7ΔMPC不能形成肌管，但能促进脂肪生成。严重肢体威胁缺血患者的骨骼肌在更多的缺血区脂肪增加，这与较少的卫星细胞相对应。总之，这些数据表明，Pax7+MPC是缺血后肌肉再生所必需的，并提示肌肉再生可能是PAD的一个重要治疗靶点。
Skeletal muscle injury in peripheral artery disease (PAD) has been attributed to vascular insufficiency, however evidence has demonstrated that muscle cell responses play a role in determining outcomes in limb ischemia. Here, we demonstrate that genetic ablation of Pax7+ muscle progenitor cells (MPCs) in a model of hindlimb ischemia (HLI) inhibited muscle regeneration following ischemic injury, despite a lack of morphological or physiological changes in resting muscle. Compared to control mice (Pax7WT), the ischemic limb of Pax7-deficient mice (Pax7Δ) was unable to generate significant force 7 or 28 days after HLI. A significant increase in adipose was observed in the ischemic limb 28 days after HLI in Pax7Δ mice, which replaced functional muscle. Adipogenesis in Pax7Δ mice corresponded with a significant increase in PDGFRα+ fibro/adipogenic progenitors (FAPs). Inhibition of FAPs with batimastat decreased muscle adipose but increased fibrosis. In vitro, Pax7Δ MPCs failed to form myotubes but displayed increased adipogenesis. Skeletal muscle from patients with critical limb threatening ischemia displayed increased adipose in more ischemic regions of muscle, which corresponded with fewer satellite cells. Collectively, these data demonstrate that Pax7+ MPCs are required for muscle regeneration after ischemia and suggest that muscle regeneration may be an important therapeutic target in PAD.
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影响因子：
168.9
作者：
Fowkes, F. Gerald R.;Rudan, Diana;Criqui, Michael H.
通讯作者：
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影响因子：
3.7
作者：
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影响因子：
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作者：
Gignac PM;Kley NJ;Clarke JA;Colbert MW;Morhardt AC;Cerio D;Cost IN;Cox PG;Daza JD;Early CM;Echols MS;Henkelman RM;Herdina AN;Holliday CM;Li Z;Mahlow K;Merchant S;Müller J;Orsbon CP;Paluh DJ;Thies ML;Tsai HP;Witmer LM
通讯作者：
Witmer LM
影响因子：
8.6
作者：
Connell, Justin G.;Genorio, Bostjan;Markovic, Nenad M.
通讯作者：
Markovic, Nenad M.
DOI：
10.1016/j.ejvs.2017.07.005
发表时间：
2017-10-01
影响因子：
5.7
作者：
Fridh, E. Baubeta;Andersson, M.;Nordanstig, J.
通讯作者：
Nordanstig, J.