Epidermal-Derived Hedgehog Signaling Drives Mesenchymal Proliferation during Digit Tip Regeneration.
Epidermal-Derived Hedgehog Signaling Drives Mesenchymal Proliferation during Digit Tip Regeneration.
复制标题
DOI：
10.3390/jcm10184261
复制
发表时间：
2021-09-20
影响因子：
3.9
通讯作者：
Gurtner GC
中科院分区：
文献类型：
--
作者：
Maan ZN;Rinkevich Y;Barrera J;Chen K;Henn D;Foster D;Bonham CA;Padmanabhan J;Sivaraj D;Duscher D;Hu M;Yan K;Januszyk M;Longaker MT;Weissman IL;Gurtner GC
手部损伤通常会导致严重的功能障碍，很少能完全恢复。例如，在蝾螈和蝾螈中发生的受伤附肢的自发再生，在远端截肢后的人类指尖中也有报道，但这种类型的再生在哺乳动物中很少见，而且还不完全了解。在这里，我们研究指尖再生切断小鼠指尖，无论是远端启动再生，或近端，造成纤维化。使用无偏的微阵列分析，我们发现，指尖再生与毛囊分化，Wnt，和音刺猬（SHH）信号通路显着相关。病毒过表达和基因敲除显示了这些途径在再生过程中的功能意义。使用转基因报告小鼠，我们证明，虽然经典的Wnt和HH信号仅限于表皮组织，下游刺猬信号（通过Gli）发生在间充质组织。这些发现揭示了表皮/间充质相互作用的机制，由典型的刺猬信号，在手指再生。对这些途径的进一步研究可能会改善人类手部受伤后的治疗效果。
Hand injuries often result in significant functional impairments and are rarely completely restored. The spontaneous regeneration of injured appendages, which occurs in salamanders and newts, for example, has been reported in human fingertips after distal amputation, but this type of regeneration is rare in mammals and is incompletely understood. Here, we study fingertip regeneration by amputating murine digit tips, either distally to initiate regeneration, or proximally, causing fibrosis. Using an unbiased microarray analysis, we found that digit tip regeneration is significantly associated with hair follicle differentiation, Wnt, and sonic hedgehog (SHH) signaling pathways. Viral over-expression and genetic knockouts showed the functional significance of these pathways during regeneration. Using transgenic reporter mice, we demonstrated that, while both canonical Wnt and HH signaling were limited to epidermal tissues, downstream hedgehog signaling (through Gli) occurred in mesenchymal tissues. These findings reveal a mechanism for epidermal/mesenchyme interactions, governed by canonical hedgehog signaling, during digit regeneration. Further research into these pathways could lead to improved therapeutic outcomes after hand injuries in humans.
登录
查看更多内容
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
4.4
作者：
Khan I;Maldonado E;Vasconcelos V;O'Brien SJ;Johnson WE;Antunes A
通讯作者：
Antunes A
影响因子：
10.5
作者：
de Lau W;Peng WC;Gros P;Clevers H
通讯作者：
Clevers H
影响因子：
4.8
作者：
Aarabi, Shahram;Bhatt, Kirit A.;Gurtner, Geoffrey C.
通讯作者：
Gurtner, Geoffrey C.
影响因子：
4
作者：
Karlsen, Tommy A.;Jakobsen, Rune B.;Brinchmann, Jan E.
通讯作者：
Brinchmann, Jan E.