Platelet-derived growth factor C plays a role in the branchial arch malformations induced by retinoic acid |
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Authors: | Han Jing Li Li Zhang Zhaofeng Xiao Ying Lin Jiuxiang Zheng Liping Li Yong |
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Institution: | Department of Food Science and Nutrition, School of Public Health, Peking University, Beijing, China. |
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Abstract: | BACKGROUND: All-trans-retinoic acid (RA) can produce branchial arch abnormalities in postimplantation rodent embryos cultured in vitro. Platelet-derived growth factor C (PDGF-C) was recently identified as a member of the PDGF ligand family. Many members of the PDGF family are essential for branchial arch morphogenesis and can be regulated by RA. The roles of PDGF-C in branchial arch malformations induced by RA and possible mechanisms were investigated. METHODS: In whole embryo culture (WEC), mouse embryos were exposed to RA at 0, 0.1, 0.4, 1.0, or 10.0 microM, PDGF-C at 25, 50, or 75 ng/mL, or PDGF-C at 25, 50, or 75 ng/mL containing 0.4 microM RA. After 48 h of culture, mouse embryos were examined for dysmorphogenesis, and whole-mount immunohistochemistry was applied to PDGF-C. In explant cultures, explants were exposed to the same doses of RA and PDGF-C as WEC. Semiquantitative RT-PCR, zymography, and reverse zymography were used to evaluate the expressions and activities of matrix metalloproteinase (MMP)-2, MMP-14, and tissue inhibitor of metalloproteinase (TIMP)-2. RESULTS: PDGF-C was reduced by RA, and exogenous PDGF-C rescued the branchial arch malformations induced by RA. Moreover, PDGF-C prevented RA-induced inhibition of the migratory ability of mesenchymal cells in the first branchial arch, by regulating the expressions of MMP-2, MMP-14, and TIPM-2. CONCLUSIONS: Our results suggest that RA exposure reduces the expression of PDGF-C. The branchial arch malformations resulting from fetal RA exposure are caused at least partially by loss of PDGF-C and subsequent misregulations of the expressions of MMP-2, MMP-14, and TIMP-2. |
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Keywords: | PDGF‐C all‐trans‐retinoic acid branchial arch morphogenesis MMP‐2 MMP‐14 TIMP‐2 craniofacial development cell migration |
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