AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylate...AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.展开更多
Focal cortical dysplasia(FCD)is an important cause of intractable epilepsy,with FCD type Ⅱ(FCD Ⅱ)being the most common subtype.FCD Ⅱ is characterized by cortical dyslamination accompanied by dysmorphic neurons(DNs)...Focal cortical dysplasia(FCD)is an important cause of intractable epilepsy,with FCD type Ⅱ(FCD Ⅱ)being the most common subtype.FCD Ⅱ is characterized by cortical dyslamination accompanied by dysmorphic neurons(DNs).Identifying the molecular alterations and targetable biomarkers is pivotal for developing therapies.Here,we provide a detailed description of the neuropathological manifestations of FCD Ⅱ,including morphological alterations and immunophenotypic profiles,indicating that abnormal cells exhibit a diverse spectrum of mixed differentiation states.Furthermore,we summarize current research on the pathogenetic mechanisms,indicating that gene mutations,epigenetic alterations,cortical developmental protein disturbances,inflammatory processes,and extrinsic damages may lead to abnormal neuronal proliferation and migration,thereby contributing to the emergence and progression of FCD Ⅱ.These findings not only enhance our understanding of the pathogenesis of FCD Ⅱ but also offer new directions for clinical diagnosis and treatment.Future research should further explore the interactions among these factors and employ multidisciplinary approaches to advance our understanding of FCD Ⅱ.展开更多
基金Supported by National Natural Science Foundation of China (No.81100649)
文摘AIMTo investigate whether the abnormal differentiation of the pterygium epithelium is related to the extracellular signal-regulated kinase (ERK) signaling pathway in vitro.METHODSThe expression levels of phosphorylated ERK (P-ERK), keratin family members including K19 and K10 and the ocular master control gene Pax-6 were measured in 16 surgically excised pterygium tissues and 12 eye bank conjunctiva. In colony-forming cell assays, the differences in clone morphology and in K10, K19, P-ERK and Pax-6 expression between the head and body were investigated. When cocultured with the ERK signaling pathway inhibitor PD98059, the changes in clone morphology, colony-forming efficiency, differentiated marker K10, K19 and Pax-6 expression and P-ERK protein expression level were examined by immunoreactivity and Western blot analysis.RESULTSThe expression of K19 and Pax-6 decreased in the pterygium, especially in the head. No staining of K10 was found in the normal conjunctiva epithelium, but it was found to be expressed in the superficial cells in the head of the pterygium. Characteristic upregulation of P-ERK was observed by immunohistochemistry. The clone from the head with more differentiated cells in the center expressed more K10, and the clone from the body expressed more K19. The P-ERK protein level increased in the pterygium epithelium compared with conjunctiva and decreased when cocultured with PD98059. The same medium with the ERK inhibitor PD98059 was more effective in promoting clonal growth than conventional medium with 3T3 murine feeder layers. It was observed that the epithelium clone co-cultured with the inhibitor had decreased K10 expression and increased K19 and Pax-6 expression.CONCLUSIONWe suggest ERK signaling pathway activation might play a role in the pterygium epithelium abnormal differentiation.
基金supported by the Shenzhen Municipal Science and Technology key projects of the Basic Research Program(file no.LMZ JCYJ20220818102007015)the National Natural Science Foundation of China(file no.LMZ 82071447,82371456).
文摘Focal cortical dysplasia(FCD)is an important cause of intractable epilepsy,with FCD type Ⅱ(FCD Ⅱ)being the most common subtype.FCD Ⅱ is characterized by cortical dyslamination accompanied by dysmorphic neurons(DNs).Identifying the molecular alterations and targetable biomarkers is pivotal for developing therapies.Here,we provide a detailed description of the neuropathological manifestations of FCD Ⅱ,including morphological alterations and immunophenotypic profiles,indicating that abnormal cells exhibit a diverse spectrum of mixed differentiation states.Furthermore,we summarize current research on the pathogenetic mechanisms,indicating that gene mutations,epigenetic alterations,cortical developmental protein disturbances,inflammatory processes,and extrinsic damages may lead to abnormal neuronal proliferation and migration,thereby contributing to the emergence and progression of FCD Ⅱ.These findings not only enhance our understanding of the pathogenesis of FCD Ⅱ but also offer new directions for clinical diagnosis and treatment.Future research should further explore the interactions among these factors and employ multidisciplinary approaches to advance our understanding of FCD Ⅱ.
