AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT...AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls.The proliferation,apoptosis,cell cycle and epithelial-mesenchymal transition(EMT)of human lens epithelial cell(HLE-B3)were further analyzed under the condition of COL4A1 gene silence.Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells.RESULTS:The aberrant expression of COL4A1 was identified a clinically associated with the ARC.Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle.Moreover,COL4A1 gene silence didn’t affect the cytoskeleton of HLE-B3 but down-regulated the Collagen typeⅣAlpha 2 Chain(COL4A2),paired box 6(PAX6),procollagen-lysine 2-oxoglutarate 5-dioxygenases 1(PLOD1)and procollagenlysine 2-oxoglutarate 5-dioxygenases 2(PLOD2)expression levels in HLE-B3 cells.Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta(TGF-β)expression.CONCLUSION:Silencing of COL4A1 induces S-phase arrest,also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT,and down-regulates the expression of COL4A2,PAX6,PLOD1 and PLOD2.Thus,the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.展开更多
Ⅳ型胶原蛋白基因α1(α1type IV collagen,COL4A1)编码Ⅳ型胶原的α1链,是构成所有组织基底膜的主要成分。COL4A1基因突变可引起脑内小动脉病变,在一定的环境压力下引发脑内小血管的阻塞或破裂,造成脑出血(intracerrbral hemorrhage,I...Ⅳ型胶原蛋白基因α1(α1type IV collagen,COL4A1)编码Ⅳ型胶原的α1链,是构成所有组织基底膜的主要成分。COL4A1基因突变可引起脑内小动脉病变,在一定的环境压力下引发脑内小血管的阻塞或破裂,造成脑出血(intracerrbral hemorrhage,ICH)。本文综述了COL4A1与α1链的结构,构成IV型胶原的方式,Ⅳ型胶原在基底膜中的作用以及目前发现的COL4A1突变引发的人类脑血管方面的疾病,并对发病机理进行了简要综述。展开更多
伴或不伴眼部异常的脑小血管病1型(Brain small vessel disease 1 with or without ocular anomalies,BSVD1)是由COL4A1基因变异导致的IV型胶原蛋白异常相关的疾病[1-2]。该基因变异导致的表型谱非常广泛,包括脑白质病、脑穿通畸形、脑...伴或不伴眼部异常的脑小血管病1型(Brain small vessel disease 1 with or without ocular anomalies,BSVD1)是由COL4A1基因变异导致的IV型胶原蛋白异常相关的疾病[1-2]。该基因变异导致的表型谱非常广泛,包括脑白质病、脑穿通畸形、脑裂畸形、脑出血、脑钙化、遗传性血管病伴肾病。展开更多
基金Supported by Supporting Fund Project of Shaanxi Provincial Department of Science and Technology Agency Project(No.2022SF-502)Special Scientific Research Program of Education Department of Shaanxi Provincial Government(No.21JK0891)+1 种基金Young Talent Lifting Project of Xi’an Science and Technology Association(No.095920221365)Innovation and Entrepreneurship Training Program for College students of Xi’an Medical University(No.121521113)。
文摘AIM:To evaluate the regulation of the aberrant expression of collagen typeⅣalpha 1 chain(COL4A1)in the development of age-related cataract(ARC).METHODS:Quantitative reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot analysis were employed to evaluate the expression of COL4A1 in ARC patients and healthy controls.The proliferation,apoptosis,cell cycle and epithelial-mesenchymal transition(EMT)of human lens epithelial cell(HLE-B3)were further analyzed under the condition of COL4A1 gene silence.Alteration of gene expression at mRNA level after knockdown COL4A1 were also evaluated by qRT-PCR on HLE-B3 cells.RESULTS:The aberrant expression of COL4A1 was identified a clinically associated with the ARC.Silencing of COL4A1 promoted the apoptosis and inhibited the proliferation of HLE-B3 by blocking the cell cycle.Moreover,COL4A1 gene silence didn’t affect the cytoskeleton of HLE-B3 but down-regulated the Collagen typeⅣAlpha 2 Chain(COL4A2),paired box 6(PAX6),procollagen-lysine 2-oxoglutarate 5-dioxygenases 1(PLOD1)and procollagenlysine 2-oxoglutarate 5-dioxygenases 2(PLOD2)expression levels in HLE-B3 cells.Silencing the COL4A1 gene induced EMT of the HLE-B3 cells by promoting the transforming growth factor beta(TGF-β)expression.CONCLUSION:Silencing of COL4A1 induces S-phase arrest,also inhibits the proliferation and enhance HLE-B3 apoptosis and EMT,and down-regulates the expression of COL4A2,PAX6,PLOD1 and PLOD2.Thus,the expression alteration of COL4A1 may play a critical role in the pathogenesis of ARC.
文摘Ⅳ型胶原蛋白基因α1(α1type IV collagen,COL4A1)编码Ⅳ型胶原的α1链,是构成所有组织基底膜的主要成分。COL4A1基因突变可引起脑内小动脉病变,在一定的环境压力下引发脑内小血管的阻塞或破裂,造成脑出血(intracerrbral hemorrhage,ICH)。本文综述了COL4A1与α1链的结构,构成IV型胶原的方式,Ⅳ型胶原在基底膜中的作用以及目前发现的COL4A1突变引发的人类脑血管方面的疾病,并对发病机理进行了简要综述。
文摘伴或不伴眼部异常的脑小血管病1型(Brain small vessel disease 1 with or without ocular anomalies,BSVD1)是由COL4A1基因变异导致的IV型胶原蛋白异常相关的疾病[1-2]。该基因变异导致的表型谱非常广泛,包括脑白质病、脑穿通畸形、脑裂畸形、脑出血、脑钙化、遗传性血管病伴肾病。
