USP37稳定的SALL4通过PI3K/AKT通路促进化体的形成
Shuo Fang1, Zishuo Wang2, Jianguo Xu1
1Department of Plastic Surgery, The First Affiliated Hospital of Navy Medical University, Shanghai City, 200000, P.R. China.
Scientific reports
|March 4, 2025
概括
裂纹样转录因子4 (SALL4) 促进了 keloid 纤维细胞的生长,迁移和 ECM 积累. 乌比基特异性酶37 (USP37) 稳定了SALL4,通过PI3K/AKT通路增强了 keloid 的形成.
科学领域:
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
- 在瘤学瘤学.
背景情况:
- 裂纹样转录因子4 (SALL4) 涉及到各种人类疾病.
- 在 keloid 形成中,SALL4 的特定作用和调节机制尚不清楚.
研究的目的:
- 研究SALL4在 keloid 纤维细胞增殖,迁移,入侵,细胞外基质 (ECM) 积累和糖解中的作用和机制.
- 为了阐明SALL4和全方位素特异性酶37 (USP37) 在 keloid 病原发生过程中的相互作用.
主要方法:
- 定量实时PCR和西布洛特用于评估SALL4和USP37表达.
- 细胞测试 (CCK8,EDU,流细胞计,Transwell,伤口愈合) 来评估纤维细胞的功能.
- 同免疫沉以确认USP37-SALL4相互作用并评估途径激活.
主要成果:
- 在 keloid 组织和纤维细胞中,SALL4 表达显著上调.
- 抑制SALL4抑制了 keloid 纤维细胞的生长,入侵,迁移,ECM积累和糖解.
- USP37对SALL4进行了脱化和稳定,促进了 keloid 纤维细胞的功能.
- USP37/SALL4轴激活了PI3K/AKT通路,从而推动了 keloid 病原体的产生.
结论:
- SALL4是 keloid 纤维细胞过度增殖和 ECM 沉积的关键驱动因素.
- USP37稳定了SALL4,通过PI3K/AKT通路的激活,促进了 keloid 的形成.
- 针对USP37/SALL4轴可能为 keloid 治疗提供治疗策略.
相关概念视频
PI3K/mTOR/AKT Signaling Pathway
3.4K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.4K
The JAK-STAT Signaling Pathway
8.6K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
8.6K
MAPK Signaling Cascades
5.1K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
5.1K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
Abnormal Proliferation
4.4K
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.4K
Interactions Between Signaling Pathways
6.2K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.2K


