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Stamp 家族蛋白在脂肪细胞分化中的差异表达和功能。

Differential expression and function of stamp family proteins in adipocyte differentiation.

机构信息

Department of Biosciences, University of Oslo, Postboks, Oslo, Norway.

出版信息

PLoS One. 2013 Jul 10;8(7):e68249. doi: 10.1371/journal.pone.0068249. Print 2013.

DOI:10.1371/journal.pone.0068249
PMID:23874564
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3707909/
Abstract

Six transmembrane protein of prostate (Stamp) proteins play an important role in prostate cancer cell growth. Recently, we found that Stamp2 has a critical role in the integration of inflammatory and metabolic signals in adipose tissue where it is highly expressed and regulated by nutritional and metabolic cues. In this study, we show that all Stamp family members are differentially regulated during adipogenesis: whereas Stamp1 expression is significantly decreased upon differentiation, Stamp2 expression is increased. In contrast, Stamp3 expression is modestly changed in adipocytes compared to preadipocytes, and has a biphasic expression pattern during the course of differentiation. Suppression of Stamp1 or Stamp2 expression both led to inhibition of 3T3-L1 differentiation in concert with diminished expression of the key regulators of adipogenesis - CCAAT/enhancer binding protein alpha (C/ebpα) and peroxisome proliferator-activated receptor gamma (Pparγ). Upon Stamp1 knockdown, mitotic clonal expansion was also inhibited. In contrast, Stamp2 knockdown did not affect mitotic clonal expansion, but resulted in a marked decrease in superoxide production that is known to affect adipogenesis. These results suggest that Stamp1 and Stamp2 play critical roles in adipogenesis, but through different mechanisms.

摘要

前列腺六跨膜蛋白(Stamp)蛋白在前列腺癌细胞生长中发挥重要作用。最近,我们发现 Stamp2 在脂肪组织中炎症和代谢信号的整合中起关键作用,在脂肪组织中高表达并受营养和代谢信号的调节。在这项研究中,我们表明,所有 Stamp 家族成员在脂肪生成过程中都受到差异调控:尽管 Stamp1 的表达在分化时显著降低,但 Stamp2 的表达增加。相比之下,Stamp3 在脂肪细胞中的表达与前脂肪细胞相比变化不大,并且在分化过程中呈双相表达模式。Stamp1 或 Stamp2 的表达抑制均导致 3T3-L1 分化受到抑制,同时脂肪生成的关键调节因子 CCAAT/增强子结合蛋白α(C/ebpα)和过氧化物酶体增殖物激活受体γ(Pparγ)的表达减少。Stamp1 敲低后,有丝分裂克隆扩张也受到抑制。相比之下,Stamp2 敲低不会影响有丝分裂克隆扩张,但会导致已知影响脂肪生成的超氧化物产生明显减少。这些结果表明,Stamp1 和 Stamp2 在脂肪生成中发挥关键作用,但通过不同的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/6cfa64dadf5f/pone.0068249.g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/3db9f978d118/pone.0068249.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/692c7c4adaa9/pone.0068249.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/6cfa64dadf5f/pone.0068249.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/e5b98d5a0dcf/pone.0068249.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/aa0389641ce0/pone.0068249.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/23007e2c4528/pone.0068249.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/692c7c4adaa9/pone.0068249.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1e53/3707909/6cfa64dadf5f/pone.0068249.g007.jpg

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