HGF and bFGF Secreted by Adipose-Derived Mesenchymal Stem Cells Revert the Fibroblast Phenotype Caused by Vocal Fold Injury in a Rat Model
HGF and bFGF Secreted by Adipose-Derived Mesenchymal Stem Cells Revert the Fibroblast Phenotype Caused by Vocal Fold Injury in a Rat Model
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脂肪间充质干细胞分泌的 HGF 和 bFGF 可恢复大鼠模型中声带损伤引起的成纤维细胞表型
DOI：
10.1016/j.jvoice.2020.08.023
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发表时间：
2022-09-22
期刊：
影响因子：
2.2
通讯作者：
Xu, Wen
中科院分区：
文献类型：
--
作者：
Li, Xueyan;Wang, Haizhou;Xu, Wen
目标。探讨脂肪源性间充质干细胞（ADSCs）、分泌型肝细胞生长因子（HGF）和碱性成纤维细胞生长因子（bFGF）对声带损伤后成纤维细胞表型的影响。我们培养原代正常（未损伤）和损伤的声带成纤维细胞（vff）。体外构建ADSCs与损伤VFFs的transwell共培养体系，抑制HGF或bFGF的作用。观察vff的增殖、细胞外基质（ECM）分泌及转化情况。与未损伤VFF相比，损伤VFF的胶原分泌量显著增加，hya-luronan synthase 1 （HAS1）分泌减少，VFF转化量显著增加。与ADSCs共培养后，VFFs增殖加快，转化受到抑制。共培养抑制了I型和III型胶原的表达，促进了HAS1的表达。抑制HGF或bFGF的分泌可抑制受损vff的增殖。两组对胶原蛋白的抑制作用均降低，但抗hgf组更明显。抗bfgf组损伤后对HAS1分泌的影响较抗hgf组显著，但差异无统计学意义。损伤VFFs的转化抑制减弱，a-平滑肌肌动蛋白表达上调，抗hgf组表现更为明显。ADSCs和分泌的HGF、bFGF可恢复声带损伤后的成纤维细胞表型。HGF对胶原分泌和vff向肌成纤维细胞转化的影响比bFGF更显著。然而，bFGF在上调HAS1方面比HGF更有效。
Objective. To investigate how adipose-derived mesenchymal stem cells (ADSCs), secreted hepato-cyte growth factor (HGF), and basic fibroblast growth factor (bFGF) affect the fibroblast phenotype after vocal fold injury.Methods. We cultured primary normal (uninjured) and injured vocal fold fibroblasts (VFFs). A transwell co-culture system of ADSCs and injured VFFs was constructed in vitro , then the effects of HGF or bFGF were inhibited. The proliferation, extracellular matrix (ECM) secretion and transformation of VFFs were observed.Results. Compared with uninjured VFFs, the secretion of collagen by injured VFFs increased significantly, hya-luronan synthase 1 (HAS1) secretion decreased, and VFF transformation increased significantly. After co-culture with ADSCs, the proliferation of VFFs was accelerated and the transformation was inhibited. Co-culture inhib-ited the expression of type I and III collagen and promoted the expression of HAS1. When HGF or bFGF secre-tion was inhibited, the proliferation of injured VFFs was inhibited. The inhibitory effect on collagen was reduced by both groups, but this was more obvious with the anti-HGF group. The anti-bFGF group had a more promi-nent effect on HAS1 secretion after injury than the anti-HGF group but the difference was not statistically signifi-cant. The inhibition of the transformation of injured VFFs was reduced while a-smooth muscle actin was upregulated, which was more obvious with the anti-HGF group.Conclusions. ADSCs and secreted HGF and bFGF can revert the fibroblast phenotype caused by vocal fold injury. The effects of HGF are more significant than bFGF on collagen secretion and the transformation of VFFs into myofibroblasts. However, bFGF is more effective than HGF in upregulating HAS1.