Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.

Autor: Wu Y; Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Liu W; Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Li J; Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Shi H; Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Ma S; Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Wang D; Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Pan B; Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Xiao R; Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.; Key Laboratory of External Tissue and Organ Regeneration, Chinese Academy of Medical Sciences, Beijing, China., Jiang H; Department of Auricular Reconstruction, Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China., Liu X; Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, China.; Key Laboratory of External Tissue and Organ Regeneration, Chinese Academy of Medical Sciences, Beijing, China.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Jun; Vol. 28 (11), pp. e18443.
DOI: 10.1111/jcmm.18443
Abstrakt: The human auricle has a complex structure, and microtia is a congenital malformation characterized by decreased size and loss of elaborate structure in the affected ear with a high incidence. Our previous studies suggest that inadequate cell migration is the primary cytological basis for the pathogenesis of microtia, however, the underlying mechanism is unclear. Here, we further demonstrate that microtia chondrocytes show a decreased directional persistence during cell migration. Directional persistence can define a leading edge associated with oriented movement, and any mistakes would affect cell function and tissue morphology. By the screening of motility-related genes and subsequent confirmations, active Rac1 (Rac1-GTP) is identified to be critical for the impaired directional persistence of microtia chondrocytes migration. Moreover, Rho guanine nucleotide exchange factors (GEFs) and Rho GTPase-activating proteins (GAPs) are detected, and overexpression of Tiam1 significantly upregulates the level of Rac1-GTP and improves directional migration in microtia chondrocytes. Consistently, decreased expression patterns of Tiam1 and active Rac1 are found in microtia mouse models, Bmp5 se /J and Prkra lear -3J/GrsrJ. Collectively, our results provide new insights into microtia development and therapeutic strategies of tissue engineering for microtia patients.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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