Fang Chien-Liang, Huang Ling-Hung, Tsai Hung-Yueh, Chang Hsin-I
Division of Plastic and Reconstructive Surgery, Department of Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, No. 539, Zhongxiao Rd., Chiayi City 60002, Taiwan.
Department of Biochemical Science and Technology, National Chia Yi University, No. 300, Syuefu Rd., Chiayi City 60004, Taiwan.
Int J Mol Sci. 2016 Jul 14;17(7):1129. doi: 10.3390/ijms17071129.
Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts.
脂联素是皮下脂肪中含量最丰富的脂肪因子之一，通过内分泌、旁分泌或自分泌机制调节多种活动。然而，其在脂肪生成诱导的成纤维细胞中的表达以及在光老化中的潜在作用尚未确定。在此，人真皮成纤维细胞Hs68被用作通过脂肪生成分化培养基（ADM）刺激的真皮脂肪生成细胞模型。与在小鼠前脂肪细胞模型（即3T3-L1）中的其他研究类似，Hs68成纤维细胞基于脂质积累、甘油三酯形成以及PPAR-γ、脂蛋白脂肪酶（LPL）和FABP4 mRNA的表达表现出脂肪生成倾向。正如预期的那样，ADM处理的成纤维细胞脂联素表达降低。接下来，我们强调了脂联素对Hs68成纤维细胞中UVA诱导损伤的光保护作用。UVA辐射可下调Hs68成纤维细胞的细胞黏附强度和弹性模量。此外，UVA辐射可诱导表皮生长因子受体（EGFR）、脂联素受体1（AdipoR1）、基质金属蛋白酶-1（MMP-1）、MMP-3和环氧化酶-2（COX-2）的mRNA表达，但下调I型和III型胶原的mRNA表达。另一方面，脂联素后处理可通过激活AdipoR1和抑制EGF-R部分克服UVA诱导的Hs68成纤维细胞细胞黏附强度降低。此外，脂联素后处理表明III型胶原和弹性蛋白mRNA表达增加，MMP-1和MMP-3 mRNA表达降低，但UVA照射的Hs68成纤维细胞的弹性模量恢复程度有限。总体而言，这些结果表明真皮脂肪生成可能抑制脂联素的表达，而外源性给予脂联素可防止Hs68成纤维细胞中UVA诱导的真皮基质降解。
