Down-regulation of polycystin in lymphatic malformations: possible role in the proliferation of lymphatic endothelial cells

Autor: Jie-Gang Yang, Yi-Fang Zhao, Gang Chen, Jun-Yi Zhu, Wei Zhang, Yanfang Sun, Ji-Hong Zhao, Hou-Fu Xia, Jian-Gang Ren
Rok vydání: 2017
Předmět:
0301 basic medicine
MAPK/ERK pathway
Pathology
medicine.medical_specialty
TRPP Cation Channels
government.form_of_government
Down-Regulation
Fluorescent Antibody Technique
Biology
Real-Time Polymerase Chain Reaction
Pathology and Forensic Medicine
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Lymphatic vessel
medicine
Cluster Analysis
Humans
Lymphangiogenesis
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Cell Proliferation
Lymphatic Vessels
Cell growth
Reverse Transcriptase Polymerase Chain Reaction
Endothelial Cells
Cell biology
Lymphatic Endothelium
030104 developmental biology
Lymphatic system
medicine.anatomical_structure
Ki-67 Antigen
030220 oncology & carcinogenesis
Case-Control Studies
government
Signal transduction
Endothelium
Lymphatic
Biomarkers
Signal Transduction
Zdroj: Human pathology. 65
ISSN: 1532-8392
Popis: Lymphatic malformations (LMs) are composed of aberrant lymphatic vessels and regarded as benign growths of the lymphatic system. Recent studies have demonstrated that the mutant embryos of PKD1 and PKD2, encoding polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively, result in aberrant lymphatic vessels similar to those observed in LMs. In this study, for the first time, we investigated PC-1 and PC-2 expression and assessed their roles in the development of LMs. Our results demonstrated that PC-1 and PC-2 gene and protein expressions were obviously decreased in LMs compared with normal skin tissues. In addition, the expression of phosphorylated ERK but not total ERK was up-regulated in LMs and negatively correlated with the expression of PC-1 and PC-2. Moreover, up-regulation of Ki67 was detected in LMs and positively correlated with ERK phosphorylation levels. Furthermore, cluster analysis better reflected close correlation between these signals. All of the above results provided strong evidence suggesting that the hyperactivation of the ERK pathway may be caused by down-regulation of PC-1 and PC-2 in LMs, contributing to increased proliferation of lymphatic endothelial cells in LMs. Our present study sheds light on novel potential mechanisms involved in LMs and may help to explore novel treatments for LMs.
Databáze: OpenAIRE
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