Sprr2h,全称为Small proline-rich protein 2h,是一种小脯氨酸富集蛋白。这类蛋白是角化细胞包膜(Cornified cell envelope, CE)的主要成分,CE是一种高度不溶性的结构,由共价交联的蛋白质组成,对于形成皮肤的保护屏障至关重要[7]。Sprr2h通过与其他蛋白质和脂质相互作用,帮助维持皮肤的屏障功能,防止水分和离子的流失,并保护身体免受环境危害。
Sprr2h的表达受到多种因素的调控。例如,在缺乏角蛋白的动物模型中,Sprr2h的表达会被上调,以补偿CE的主要蛋白角蛋白的缺失[1]。此外,Sprr2h的表达还受到Nrf2(NF-E2相关因子2)的调控,Nrf2是一种转录因子,在响应氧化应激时被激活[5]。在缺乏loricrin的动物模型中,Sprr2h的表达也会被上调,以补偿CE的缺失[7]。
Sprr2h的表达还与眼表功能有关。在NHE8(钠/氢交换器8)缺失的动物模型中,Sprr2h的表达上调,这表明Sprr2h可能在维持眼表功能方面发挥作用[2]。此外,在Spdef(SAM-pointed domain epithelial-specific transcription factor)缺失的动物模型中,Sprr2h的表达也上调,这表明Sprr2h可能与干眼症的发生有关[4]。
Sprr2h的表达还与肿瘤的发生有关。在肿瘤促进剂TPA诱导的鼠JB6 P+细胞中,Sprr2h的表达上调,这表明Sprr2h可能在肿瘤的发生中发挥作用[6]。此外,在PRL8A2(Prolactin family 8, subfamily a, member 2)缺失的动物模型中,Sprr2h的表达下调,这表明Sprr2h可能与妊娠相关的适应有关[3]。
总的来说,Sprr2h是一种重要的蛋白质,参与维持皮肤的屏障功能和眼表功能,并与肿瘤的发生和妊娠相关适应有关。Sprr2h的研究有助于深入理解Sprr2h的生物学功能和疾病发生机制,为疾病的治疗和预防提供新的思路和策略。
参考文献:
1. Kumar, Vinod, Bouameur, Jamal-Eddine, Bär, Janina, Seibel, Peter, Magin, Thomas M. . A keratin scaffold regulates epidermal barrier formation, mitochondrial lipid composition, and activity. In The Journal of cell biology, 211, 1057-75. doi:10.1083/jcb.201404147. https://pubmed.ncbi.nlm.nih.gov/26644517/
2. Xu, Hua, Zhao, Yang, Li, Jing, Gao, Minghong, Ghishan, Fayez K. 2014. Loss of NHE8 expression impairs ocular surface function in mice. In American journal of physiology. Cell physiology, 308, C79-87. doi:10.1152/ajpcell.00296.2014. https://pubmed.ncbi.nlm.nih.gov/25377091/
3. Alam, S M Khorshed, Konno, Toshihiro, Soares, Michael J. . Identification of target genes for a prolactin family paralog in mouse decidua. In Reproduction (Cambridge, England), 149, 625-32. doi:10.1530/REP-15-0107. https://pubmed.ncbi.nlm.nih.gov/25926690/
4. Marko, Christina K, Menon, Balaraj B, Chen, Gang, Clevers, Hans, Gipson, Ilene K. 2013. Spdef null mice lack conjunctival goblet cells and provide a model of dry eye. In The American journal of pathology, 183, 35-48. doi:10.1016/j.ajpath.2013.03.017. https://pubmed.ncbi.nlm.nih.gov/23665202/
5. Ishitsuka, Yosuke, Huebner, Aaron J, Rice, Robert H, Steven, Alasdair C, Roop, Dennis R. 2016. Lce1 Family Members Are Nrf2-Target Genes that Are Induced to Compensate for the Loss of Loricrin. In The Journal of investigative dermatology, 136, 1656-1663. doi:10.1016/j.jid.2016.04.022. https://pubmed.ncbi.nlm.nih.gov/27167730/
6. Hudlikar, Rasika R, Sargsyan, Davit, Wu, Renyi, Zheng, Meinizi, Kong, Ah-Ng. 2020. Triterpenoid corosolic acid modulates global CpG methylation and transcriptome of tumor promotor TPA induced mouse epidermal JB6 P+ cells. In Chemico-biological interactions, 321, 109025. doi:10.1016/j.cbi.2020.109025. https://pubmed.ncbi.nlm.nih.gov/32135139/
7. Koch, P J, de Viragh, P A, Scharer, E, Steven, A C, Roop, D R. . Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. In The Journal of cell biology, 151, 389-400. doi:. https://pubmed.ncbi.nlm.nih.gov/11038185/