Polarization of ADAM17-driven EGFR signalling in electric field-guided collective migration of epidermal sheets.
Polarization of ADAM17-driven EGFR signalling in electric field-guided collective migration of epidermal sheets.
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DOI：
10.1111/jcmm.16019
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发表时间：
2020-12
影响因子：
5.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Jia N;Liu J;Zhu G;Liang Y;Wang Y;Wang W;Chen Y;Yang J;Zhang W;Zhang J
内源性电场被认为在促进表皮集体迁移到伤口中心中起重要作用。然而，目前大多数研究都集中在生物电场对单个上皮细胞运动和迁移的影响上，而关于表皮细胞集体迁移的分子机制尚不清楚。在这里，我们发现EFs显着促进HaCaT细胞向阳极的集体迁移，激活ADAM 17的脱落酶活性，并增加EGFR的磷酸化水平。此外，EGFR磷酸化和HB-EGF脱落水平在EF下被ADAM 17抑制剂TAPI-2或siADAM 17显著降低，随后减弱HaCaT片层的定向迁移。值得注意的是，siADAM 17对EF调节的集体迁移的抑制通过添加重组HB-EGF而被拯救。此外，我们观察到F‐actin在EFs下沿着迁移片的前缘动态极化沿着，并且这种极化受到ADAM 17/HB‐EGF/EGFR信号转导的调节。总之，我们的研究表明，ADAM 17通过驱动HB-EGF释放和激活EFs下的EGFR，促进了表皮单层的集体定向运动，并且该途径还介导了迁移片层中F-肌动蛋白的极化，这在定向迁移中至关重要。
Endogenous electric field is considered to play an important role in promoting collective migration of epidermis to the wound centre. However, most studies are focused on the effect of bioelectric field on the movement and migration of single epithelial cell; the molecular mechanisms about collective migration of epidermal monolayers remain unclear. Here, we found that EFs dramatically promoted the collective migration of HaCaT cells towards the anode, activated the sheddase activity of ADAM17 and increased the phosphorylation level of EGFR. Moreover, EGFR phosphorylation and HB‐EGF shedding level were significantly decreased by the ADAM17 inhibitor TAPI‐2 or siADAM17 under EFs, which subsequently attenuated the directed migration of HaCaT sheets. Notably, the inhibition of EF‐regulated collective migration by siADAM17 was rescued by addition of recombinant HB‐EGF. Furthermore, we observed that F‐actin was dynamically polarized along the leading edge of the migrated sheets under EFs and that this polarization was regulated by ADAM17/HB‐EGF/EGFR signalling. In conclusion, our study indicated that ADAM17 contributed to the collective directional movement of the epidermal monolayer by driving HB‐EGF release and activating EGFR under EFs, and this pathway also mediated the polarization of F‐actin in migrating sheets, which is essential in directional migration.
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影响因子：
5.3
作者：
Meng, Xiaoting;Arocena, Miguel;Penninger, Josef;Gage, Fred H.;Zhao, Min;Song, Bing
通讯作者：
Song, Bing
影响因子：
3.5
作者：
Brooke, Matthew A.;Etheridge, Sarah L.;Kelsell, David P.
通讯作者：
Kelsell, David P.
DOI：
10.1073/pnas.1302553110
发表时间：
2013-07-09
影响因子：
11.1
作者：
Maretzky, Thorsten;McIlwain, David R.;Blobel, Carl P.
通讯作者：
Blobel, Carl P.
影响因子：
4.8
作者：
Sommer, Anselm;Fries, Anja;Reiss, Karina
通讯作者：
Reiss, Karina
影响因子：
3.3
作者：
Cho Y;Son M;Jeong H;Shin JH
通讯作者：
Shin JH