The role of SFRP1 in human dermal papilla cell growth and its potential molecular mechanisms as a target in regenerative therapy

IF 3.4 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Regenerative Therapy Pub Date : 2024-12-16 DOI:10.1016/j.reth.2024.12.001

Chaofan Wang , Yimei Du , Changpei Lu , Lingbo Bi , Yunbu Ding , Weixin Fan

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Abstract

Background

Secreted frizzled-related protein 1 (SFRP1) inhibits Wnt signaling and is differentially expressed in human hair dermal papilla cells (DPCs). However, the specific effect of SFRP1 on cell function remains unclear. Telomerase reverse transcriptase (TERT) representing telomerase activity was found highly active around the hair dermal papilla. TERT levels can be enhanced by activation of the Wnt pathway in cancer cells and embryonic stem cells. Whether this regulatory mechanism is still present in DPCs has not been studied so far.

Methods

In this study, DNA plasmids and siRNAs were constructed against the SFRP1 gene and transfected into DPCs cultured in vitro. We detected the viability, proliferation, and migration of DPCs by Calcein/PI fluorescence, CCK-8, trans-well, or cell scratch experiments, and the expression of potential target genes was also determined through quantitative detection of RNA and protein.

Results

The results demonstrate a significant difference in SFRP1 levels from the control group, suggesting successful transfection of the DNA plasmid and siRNA of SFRP1 into IDPCs. Also, SFRP1 regulates the cell proliferation capacity of IDPCs and reduces their migration functions. The DPCs' living activity, proliferation, and migration function exhibited a negative correlation with the level of SFRP1. SFPR1 also inhibits the protein or RNA expression of β-catenin and TERT in DPCs.

Conclusion

It was proven that in human DPCs, different levels of SFRP1 change how cells work and control Wnt/β-catenin signaling or telomerase activity. This means that blocking SFRP1 could become a new way to treat hair loss diseases in the future.

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SFRP1在人真皮乳头细胞生长中的作用及其作为再生治疗靶点的潜在分子机制。

背景：分泌卷曲相关蛋白1 （SFRP1）抑制Wnt信号，并在人毛真皮乳头细胞（DPCs）中差异表达。然而，SFRP1对细胞功能的具体影响尚不清楚。代表端粒酶活性的端粒酶逆转录酶（TERT）在毛发真皮乳头周围高度活跃。癌细胞和胚胎干细胞中的TERT水平可以通过激活Wnt通路而增强。这种调控机制是否仍然存在于DPCs中，目前还没有研究。方法：构建针对SFRP1基因的DNA质粒和sirna，转染到体外培养的DPCs中。我们通过Calcein/PI荧光、CCK-8、trans-well、cell scratch实验检测DPCs的活力、增殖和迁移，并通过RNA和蛋白的定量检测检测潜在靶基因的表达。结果：结果显示，与对照组相比，SFRP1的水平有显著差异，表明SFRP1的DNA质粒和siRNA成功转染到IDPCs中。此外，SFRP1调节idpc的细胞增殖能力，降低其迁移功能。DPCs的活活性、增殖和迁移功能与SFRP1水平呈负相关。SFPR1还能抑制DPCs中β-catenin和TERT蛋白或RNA的表达。结论：在人DPCs中，不同水平的SFRP1改变细胞的工作方式并控制Wnt/β-catenin信号传导或端粒酶活性。这意味着阻断SFRP1可能成为未来治疗脱发疾病的新方法。

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来源期刊

Regenerative Therapy Engineering-Biomedical Engineering

CiteScore

6.00

自引率

2.30%

发文量

106

审稿时长

49 days

期刊介绍： Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.