PLEKHH2(pleckstrin homology domain containing, family H (with FHA and coiled-coil domains) 2)是一种包含PLEKSTRAIN同源结构域的基因,具有FHA(forkhead-associated)和卷曲螺旋结构域。PLEKHH2主要在肾小球中表达,尤其是在肾小球足细胞中。PLEKHH2的表达和亚细胞分布研究表明,PLEKHH2的mRNA和蛋白质在肾小球足细胞中特异性表达,并在裂孔隔膜和足突中定位。PLEKHH2的表达模式表明,PLEKHH2可能参与肾小球生理和病理过程[7]。
PLEKHH2在多种生物学过程中发挥作用,包括免疫调节、细胞信号传导和细胞骨架重塑。PLEKHH2在免疫调节中的作用尚不清楚,但在一项研究中,PLEKHH2和CD274基因被鉴定为免疫相关基因,并发现PLEKHH2基因的突变与羊的血液生理指标有关[1]。此外,PLEKHH2基因的突变也与糖尿病肾病的发生发展相关[6]。PLEKHH2的这些发现表明,PLEKHH2可能在免疫调节和疾病发生中发挥作用。
PLEKHH2基因的突变还与某些肿瘤的发生相关。例如,PLEKHH2基因的融合基因PLEKHH2-ALK在肺腺癌中被发现,并且PLEKHH2-ALK融合基因阳性的肿瘤对ALK抑制剂治疗有较好的反应[4,5]。此外,PLEKHH2基因的融合基因PLEKHH2-ALK还在一些儿童非肌纤维母细胞样原始梭形细胞肿瘤中被发现,并且这些肿瘤对ALK抑制剂治疗有较好的反应[3]。这些发现表明,PLEKHH2基因的突变可能与某些肿瘤的发生和进展相关,并且PLEKHH2-ALK融合基因可能是这些肿瘤的潜在治疗靶点。
PLEKHH2基因的突变还与一些皮肤肿瘤的发生相关。例如,PLEKHH2基因的融合基因PLEKHH2-ALK在一些先天性头皮皮肤纤维肉瘤中已被发现,并且Mohs显微手术对这些肿瘤有较好的治疗效果[2]。此外,PLEKHH2基因的融合基因PLEKHH2-ALK在一些ALK重排、CD34阳性梭形细胞肿瘤中被发现,并且这些肿瘤对ALK抑制剂治疗有较好的反应[8]。这些发现表明,PLEKHH2基因的突变可能与某些皮肤肿瘤的发生和进展相关,并且PLEKHH2-ALK融合基因可能是这些肿瘤的潜在治疗靶点。
综上所述,PLEKHH2是一种在肾小球中特异性表达的基因,参与多种生物学过程,包括免疫调节、细胞信号传导和细胞骨架重塑。PLEKHH2基因的突变与糖尿病肾病、肺腺癌和皮肤肿瘤的发生发展相关,并且PLEKHH2-ALK融合基因可能是这些肿瘤的潜在治疗靶点。PLEKHH2的研究有助于深入理解PLEKHH2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. Zhang, Yukun, Zhang, Xiaoxue, Li, Fadi, Wang, Jianghui, Wang, Weimin. 2023. Expression profiles of the CD274 and PLEKHH2 gene and association of its polymorphism with hematologic parameters in sheep. In Veterinary immunology and immunopathology, 259, 110597. doi:10.1016/j.vetimm.2023.110597. https://pubmed.ncbi.nlm.nih.gov/37094535/
2. Ward, Rachel E, Stultz, Todd W, Billings, Steven D, Vidimos, Allison T. 2023. Mohs Micrographic Surgery for Congenital Scalp Dermatofibrosarcoma Protuberans With Novel PLEKHH2-ALK Gene Fusion. In Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.], 50, 291-293. doi:10.1097/DSS.0000000000004052. https://pubmed.ncbi.nlm.nih.gov/38085025/
3. Rakheja, Dinesh, Park, Jason Y, Fernandes, Neil J, Laetsch, Theodore W, Collins, Rebecca R J. 2022. Pediatric Non-Myofibroblastic Primitive Spindle Cell Tumors with ALK Gene Rearrangements and Response to Crizotinib. In International journal of surgical pathology, 30, 706-715. doi:10.1177/10668969221080072. https://pubmed.ncbi.nlm.nih.gov/35164578/
4. Nagasaka, Misako, Fisher, Amanda, Chowdhury, Tahmida, Ge, Yubin, Sukari, Ammar. 2020. PLEKHH2-ALK: A Novel In-frame Fusion With Durable Response to Alectinib: Utilizing RNA Sequencing in Search for Hidden Gene Fusions Susceptible to Targeted Therapy. In Clinical lung cancer, 22, e51-e53. doi:10.1016/j.cllc.2020.07.017. https://pubmed.ncbi.nlm.nih.gov/32893122/
5. Coppock, Joseph D, Schneider, Michael A, Surrey, Lea F, Maki, Robert G, Cooper, Kumarasen. 2022. S100 and CD34 Expressing Mesenchymal Neoplasm With Rare PLEKHH2::ALK Fusion and Response to ALK Inhibition. In The American journal of surgical pathology, 46, 1309-1313. doi:10.1097/PAS.0000000000001887. https://pubmed.ncbi.nlm.nih.gov/35288525/
6. Greene, Christopher N, Keong, Lisa M, Cordovado, Suzanne K, Mueller, Patricia W. 2008. Sequence variants in the PLEKHH2 region are associated with diabetic nephropathy in the GoKinD study population. In Human genetics, 124, 255-62. doi:10.1007/s00439-008-0548-y. https://pubmed.ncbi.nlm.nih.gov/18752002/
7. Patrakka, Jaakko, Xiao, Zhijie, Nukui, Masatoshi, Betsholtz, Christer, Tryggvason, Karl. 2007. Expression and subcellular distribution of novel glomerulus-associated proteins dendrin, ehd3, sh2d4a, plekhh2, and 2310066E14Rik. In Journal of the American Society of Nephrology : JASN, 18, 689-97. doi:. https://pubmed.ncbi.nlm.nih.gov/17251388/
8. Agrawal, Shruti, Ameline, Baptiste, Folpe, Andrew L, Billings, Steven D, Fritchie, Karen J. 2024. ALK-rearranged, CD34-positive spindle cell neoplasms resembling dermatofibrosarcoma protuberans: a study of seven cases. In Histopathology, 85, 649-659. doi:10.1111/his.15239. https://pubmed.ncbi.nlm.nih.gov/38867577/