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SPARC 在年轻皮肤中高表达，并通过 TGF-β 信号通路促进成纤维细胞细胞外基质的完整性。

SPARC Is Highly Expressed in Young Skin and Promotes Extracellular Matrix Integrity in Fibroblasts via the TGF-β Signaling Pathway.

机构信息

Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.

Department of Dermatology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Jul 29;24(15):12179. doi: 10.3390/ijms241512179.

DOI:10.3390/ijms241512179
PMID:37569556
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10419001/
Abstract

The matricellular secreted protein acidic and rich in cysteine (SPARC; also known as osteonectin), is involved in the regulation of extracellular matrix (ECM) synthesis, cell-ECM interactions, and bone mineralization. We found decreased SPARC expression in aged skin. Incubating foreskin fibroblasts with recombinant human SPARC led to increased type I collagen production and decreased matrix metalloproteinase-1 (MMP-1) secretion at the protein and mRNA levels. In a three-dimensional culture of foreskin fibroblasts mimicking the dermis, SPARC significantly increased the synthesis of type I collagen and decreased its degradation. In addition, SPARC also induced receptor-regulated SMAD (R-SMAD) phosphorylation. An inhibitor of transforming growth factor-beta (TGF-β) receptor type 1 reversed the SPARC-induced increase in type I collagen and decrease in MMP-1, and decreased SPARC-induced R-SMAD phosphorylation. Transcriptome analysis revealed that SPARC modulated expression of genes involved in ECM synthesis and regulation in fibroblasts. RT-qPCR confirmed that a subset of differentially expressed genes is induced by SPARC. These results indicated that SPARC enhanced ECM integrity by activating the TGF-β signaling pathway in fibroblasts. We inferred that the decline in SPARC expression in aged skin contributes to process of skin aging by negatively affecting ECM integrity in fibroblasts.

摘要

基质细胞分泌富含半胱氨酸的酸性蛋白（SPARC；也称为骨粘连蛋白）参与细胞外基质（ECM）合成、细胞-ECM 相互作用和骨矿化的调节。我们发现，衰老皮肤中 SPARC 的表达减少。将重组人 SPARC 孵育入包皮成纤维细胞中，可导致 I 型胶原蛋白的产生增加，同时 MMP-1 的蛋白和 mRNA 水平分泌减少。在模仿真皮的包皮成纤维细胞的三维培养中，SPARC 显著增加了 I 型胶原蛋白的合成，减少了其降解。此外，SPARC 还诱导了受体调节的 SMAD（R-SMAD）磷酸化。转化生长因子-β（TGF-β）受体 1 的抑制剂逆转了 SPARC 诱导的 I 型胶原蛋白增加和 MMP-1 减少，并降低了 SPARC 诱导的 R-SMAD 磷酸化。转录组分析显示，SPARC 调节了成纤维细胞中 ECM 合成和调节相关基因的表达。RT-qPCR 证实了一组差异表达基因是由 SPARC 诱导的。这些结果表明，SPARC 通过激活成纤维细胞中的 TGF-β 信号通路增强 ECM 的完整性。我们推断，衰老皮肤中 SPARC 表达的下降通过负向影响成纤维细胞中 ECM 的完整性，从而导致皮肤衰老过程。

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