Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions.
Neuropeptide substance P alters stem cell fate to aid wound healing and promote epidermal stratification through asymmetric stem cell divisions.
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神经肽 P 物质改变干细胞命运，以帮助伤口愈合并通过不对称干细胞分裂促进表皮分层。
DOI：
10.1093/stmcls/sxae009
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Ghadially,R
中科院分区：
文献类型：
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作者：
Khalifa,A;Xiao,T;Abegaze,B;Weisenberger,T;Charruyer,A;Sanad,Samia;AbuElnasr,Taher;Kashem,SW;Fassett,M;Ghadially,R
感觉神经支配的丧失延迟伤口愈合，并且神经肽物质P的施用改善上皮再形成。创伤后角质形成细胞过度增殖可能是由对称干细胞（SC）自我更新、不对称SC自我更新、定向祖细胞分裂或这些的组合引起的。然而，感觉去神经支配和神经肽对SC增殖的影响尚不清楚。在这里，我们表明，创伤后早期不对称和对称SC自我更新增加，没有显着的承诺祖（CP）激活。感觉神经支配减少与SC和CP增殖减少相关。基于先前的工作表明，物质P在辣椒素处理的小鼠中减少，并改善正常皮肤的伤口愈合，我们研究了P物质在伤口愈合过程中对SC和CP增殖的影响。物质P恢复不对称SC增殖皮肤感觉神经支配减少，无论是在基线和受伤后。感觉神经支配减少的表皮严重变薄。与此一致，P物质诱导的不对称SC增殖导致皮肤分层增加，神经支配正常和减少。拉帕替尼阻止了P物质诱导的小鼠表皮中不对称SC分裂的增加，以及表皮分层的增加，表明表皮分层需要不对称SC分裂。
Loss of sensory innervation delays wound healing and administration of the neuropeptide substance P improves re-epithelialization. Keratinocyte hyperproliferation post-wounding may result from symmetric stem cell (SC) self-renewal, asymmetric SC self-renewal, committed progenitor divisions, or a combination of these. However, the effects of sensory denervation and of neuropeptides on SC proliferation are not known. Here we show that early after wounding both asymmetric and symmetric SC self-renewal increase, without significant committed progenitor (CP) activation. Decreased sensory innervation is associated with a decrease in both SC and CP proliferation. Based on previous work showing that substance P is decreased in capsaicin-treated mice and improves wound healing in normal skin, we examined the effects of substance P on SC and CP proliferation during wound healing. Substance P restored asymmetric SC proliferation in skin with decreased sensory innervation, both at baseline and following wounding. Epidermis with decreased sensory innervation was severely thinned. Consistent with this, substance P-induced asymmetric SC proliferation resulted in increased stratification in skin with both normal and decreased innervation. Lapatinib prevented the substance P-induced increase in asymmetric SC divisions in murine epidermis, as well as the increase in epidermal stratification, suggesting that asymmetric SC divisions are required for epidermal stratification.