Objective To investigate the molecular mechanism of nectin-like molecule 1(NECL1) inhibiting the migration and invasion of U251 glioma cells.Methods We infected U251 glioma cells with adeno-nectin-like molecule 1(Ad-N...Objective To investigate the molecular mechanism of nectin-like molecule 1(NECL1) inhibiting the migration and invasion of U251 glioma cells.Methods We infected U251 glioma cells with adeno-nectin-like molecule 1(Ad-NECL1) or empty adenovirus(Ad).Transwell and wound healing assays were performed to observe the migration of U251 cells incubated with the cell supernatant from Ad-NECL1 or Ad infected U251 cells.DNA microarray was applied to screen the gene expression profile after the restoration of NECL1 in U251 glioma cell lines.The differential expression of osteopontin(OPN),a gene related to migration and invasion,was further analyzed with semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunohistochemistry.Results The restoration of NECL1 inhibited migration of U251 cells significantly(P<0.05).Altogether 195 genes were found differentially expressed by microarray,in which 175 were up-regulated and 20 down-regulated,including 9 extracellular matrix proteins involved in the migration of cells.Both mRNA and protein expressions of OPN,the most markedly reduced extracellular matrix protein,were found decreased in U251 cells after restoration of NECL1.Immunohistochemical assay also detected an increase of OPN in glioma tissues,related with the progressing of malignant grade.Conclusion A link might exist between NECL1 and the extracellular matrix protein OPN in inhibiting the migration and invasion of U251 glioma cells.展开更多
The purpose of this study was to investigate changes of β 3 integrins and extra cellular matrix proteins including fibronectin (FN), laminin (LN) and collagen type Ⅳ (CL typeⅣ) on the endometrium of secret...The purpose of this study was to investigate changes of β 3 integrins and extra cellular matrix proteins including fibronectin (FN), laminin (LN) and collagen type Ⅳ (CL typeⅣ) on the endometrium of secretory phase from 31 fertile women (fertility group)and 34 women with unexplained infertility (infertility group) by a histochemical method.The results were as follows:In glandular epithelium, β 3 integrin appeared in the mid secretory phase and continued to late secretory phase in the fertility group, but was not expressed during the secretory phase in the infertility group. Extracellular matrix proteins from the fertility group were expressed more strongly in mid secretory phase than that in the early secretory phase, and were weakest in the late secretory phase. Compared with the fertility group, the levels of extracellular matrix proteins in the infertility group were elevated in the secretory phase. In conclusion: our current study demonstrate that β 3 integrin and extracellular matrix proteins are expressed at different levels in the endometrium during the menstrual cycle. They are involved in endometrial changes during the menstrual cycle and during the implantation of the blastocyst. Their unusual expression result in the failure of implantation.展开更多
Lipoid proteinosis （LP,OMIM 247100）,also known as Urbach-Wiethe disease or lipoidosis cutis et mucosae,was first described by Urbach and Wiethe in 1929.It is a rare autosomal recessive genodermatosis characterized b...Lipoid proteinosis （LP,OMIM 247100）,also known as Urbach-Wiethe disease or lipoidosis cutis et mucosae,was first described by Urbach and Wiethe in 1929.It is a rare autosomal recessive genodermatosis characterized by hoarseness from early infancy,distinctive skin and neurological manifestations,and cutaneous lesions.It affects mucosal membranes of the upper respiratory tract,upper digestive tract,central nervous system,lymph nodes,and striated muscles.Hamada identified the genetic defect to be a loss-of-function mutation or reduced expression of the gene encoding extracellular matrix protein 1 （ECM1） on chromosome lq21 in 2002.So far,approximately,300 cases have been reported.This article reported a case with clinical and molecular findings compatible with LP.展开更多
The formation of hypertrophic scars (HSs) is a fibroproliferative disorder of abnormal wound healing. HSs usually characterize excessive proliferation of fibroblasts, abnormal deposition of extracellular matrix (ECM) ...The formation of hypertrophic scars (HSs) is a fibroproliferative disorder of abnormal wound healing. HSs usually characterize excessive proliferation of fibroblasts, abnormal deposition of extracellular matrix (ECM) during wound healing, associated with cosmetic, functional, and psychological problems. Owing to the role of ECM proteins in scar formation, we comparatively analyzed matrix proteins secreted by normal skin fibroblasts (NSFs) and HS fibroblasts (HSFs). The acetone-extracted secreted proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and identified by mass spectrometry (MS). Based on Go annotation of MS data, the profiling of ECM proteins was established and scar-related proteins have been screened out. The functions of several ECM proteins identified by MS have been discussed, such as collagens I, VI, XII, fibronectin, decorin, lumican, and protein procollagen C endopeptidase enhancer 1 (PCPE-1). Among them, the MS result of PCPE-1 was supported by Western blotting that PCPE-1 from HSFs were significantly upregulated than that from NSFs. It is suggested that PCPE-1 could be a potential target for scar treatment. The exploration of scar related proteins may provide new perspectives on understanding the mechanism of scar formation and open a new way to scar treatment and prevention.展开更多
Collagens are the most abundant proteins in mammals and form an extracellular matrix (ECM) with other components as the structural support of muscle, skin, corneas and blood vessels etc. Other than providing structura...Collagens are the most abundant proteins in mammals and form an extracellular matrix (ECM) with other components as the structural support of muscle, skin, corneas and blood vessels etc. Other than providing structural support, the ECM exhibits active communication with cells and influences many cellular processes including migration, wound healing, differentiation and cancer metastasis. Though collagen proteins contain highly repetitive primary sequences and defined tertiary structures, more and more studies have shown that many short peptides/motifs within collagen proteins play key roles in various biological processes. These short sequences are effective within triple helical structures or independently as stand-alone molecules resulting from proteolytic degradation. Besides endogenous ECM-derived peptides, many more functional peptides have been produced by tissue processing, chemical synthesis, and recombinant protein production. In this review, we summarize different peptides/motifs identified in collagen and other ECM proteins and discuss their potential for medical, personal care, and cosmetics applications.展开更多
Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, ...Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prionlike disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2 RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.展开更多
After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes ...After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.展开更多
基金Supported by National Natural Science Foundation of China (30421003,30828004)
文摘Objective To investigate the molecular mechanism of nectin-like molecule 1(NECL1) inhibiting the migration and invasion of U251 glioma cells.Methods We infected U251 glioma cells with adeno-nectin-like molecule 1(Ad-NECL1) or empty adenovirus(Ad).Transwell and wound healing assays were performed to observe the migration of U251 cells incubated with the cell supernatant from Ad-NECL1 or Ad infected U251 cells.DNA microarray was applied to screen the gene expression profile after the restoration of NECL1 in U251 glioma cell lines.The differential expression of osteopontin(OPN),a gene related to migration and invasion,was further analyzed with semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR),Western blot,and immunohistochemistry.Results The restoration of NECL1 inhibited migration of U251 cells significantly(P<0.05).Altogether 195 genes were found differentially expressed by microarray,in which 175 were up-regulated and 20 down-regulated,including 9 extracellular matrix proteins involved in the migration of cells.Both mRNA and protein expressions of OPN,the most markedly reduced extracellular matrix protein,were found decreased in U251 cells after restoration of NECL1.Immunohistochemical assay also detected an increase of OPN in glioma tissues,related with the progressing of malignant grade.Conclusion A link might exist between NECL1 and the extracellular matrix protein OPN in inhibiting the migration and invasion of U251 glioma cells.
文摘The purpose of this study was to investigate changes of β 3 integrins and extra cellular matrix proteins including fibronectin (FN), laminin (LN) and collagen type Ⅳ (CL typeⅣ) on the endometrium of secretory phase from 31 fertile women (fertility group)and 34 women with unexplained infertility (infertility group) by a histochemical method.The results were as follows:In glandular epithelium, β 3 integrin appeared in the mid secretory phase and continued to late secretory phase in the fertility group, but was not expressed during the secretory phase in the infertility group. Extracellular matrix proteins from the fertility group were expressed more strongly in mid secretory phase than that in the early secretory phase, and were weakest in the late secretory phase. Compared with the fertility group, the levels of extracellular matrix proteins in the infertility group were elevated in the secretory phase. In conclusion: our current study demonstrate that β 3 integrin and extracellular matrix proteins are expressed at different levels in the endometrium during the menstrual cycle. They are involved in endometrial changes during the menstrual cycle and during the implantation of the blastocyst. Their unusual expression result in the failure of implantation.
基金Acknowledgment We are grateful to the patient＇s family for their contribution and participation in this clinical report. We also thank our colleagues Mr. Wei Wang and Mr. Jing Xie for their help in collecting blood samples.This study was supported by a grant of National Natural Science Foundation of China （No. 81371723）.
文摘Lipoid proteinosis （LP,OMIM 247100）,also known as Urbach-Wiethe disease or lipoidosis cutis et mucosae,was first described by Urbach and Wiethe in 1929.It is a rare autosomal recessive genodermatosis characterized by hoarseness from early infancy,distinctive skin and neurological manifestations,and cutaneous lesions.It affects mucosal membranes of the upper respiratory tract,upper digestive tract,central nervous system,lymph nodes,and striated muscles.Hamada identified the genetic defect to be a loss-of-function mutation or reduced expression of the gene encoding extracellular matrix protein 1 （ECM1） on chromosome lq21 in 2002.So far,approximately,300 cases have been reported.This article reported a case with clinical and molecular findings compatible with LP.
基金We would like to thank Dr. Peter Mose Larsen for his kind suggestion to the experimental design and data analysis. This work was supported by the grants NSFC(2010ZX09401-306-4-5, 30973116 and 81171809)"863"project(2012AA020504)the State Key Laboratory Funding(SKLZZ201012)
文摘The formation of hypertrophic scars (HSs) is a fibroproliferative disorder of abnormal wound healing. HSs usually characterize excessive proliferation of fibroblasts, abnormal deposition of extracellular matrix (ECM) during wound healing, associated with cosmetic, functional, and psychological problems. Owing to the role of ECM proteins in scar formation, we comparatively analyzed matrix proteins secreted by normal skin fibroblasts (NSFs) and HS fibroblasts (HSFs). The acetone-extracted secreted proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and identified by mass spectrometry (MS). Based on Go annotation of MS data, the profiling of ECM proteins was established and scar-related proteins have been screened out. The functions of several ECM proteins identified by MS have been discussed, such as collagens I, VI, XII, fibronectin, decorin, lumican, and protein procollagen C endopeptidase enhancer 1 (PCPE-1). Among them, the MS result of PCPE-1 was supported by Western blotting that PCPE-1 from HSFs were significantly upregulated than that from NSFs. It is suggested that PCPE-1 could be a potential target for scar treatment. The exploration of scar related proteins may provide new perspectives on understanding the mechanism of scar formation and open a new way to scar treatment and prevention.
文摘Collagens are the most abundant proteins in mammals and form an extracellular matrix (ECM) with other components as the structural support of muscle, skin, corneas and blood vessels etc. Other than providing structural support, the ECM exhibits active communication with cells and influences many cellular processes including migration, wound healing, differentiation and cancer metastasis. Though collagen proteins contain highly repetitive primary sequences and defined tertiary structures, more and more studies have shown that many short peptides/motifs within collagen proteins play key roles in various biological processes. These short sequences are effective within triple helical structures or independently as stand-alone molecules resulting from proteolytic degradation. Besides endogenous ECM-derived peptides, many more functional peptides have been produced by tissue processing, chemical synthesis, and recombinant protein production. In this review, we summarize different peptides/motifs identified in collagen and other ECM proteins and discuss their potential for medical, personal care, and cosmetics applications.
文摘Amyotrophic lateral sclerosis(ALS) is a rapidly progressing neurodegenerative disease that leads to death. No effective treatments are currently available. Based on data from epidemiological, etiological, laboratory, and clinical studies, I offer a new way of thinking about ALS and its treatment. This paper describes a host of extrinsic factors, including the exposome, that disrupt the extracellular matrix and protein function such that a spreading, prionlike disease leads to neurodegeneration in the motor tracts. A treatment regimen is described using the stem cell released molecules from a number of types of adult stem cells to provide tissue dependent molecules that restore homeostasis, including proteostasis, in the ALS patient. Because stem cells themselves as a therapeutic are cumbersome and expensive, and when implanted in a host cause aging of the host tissue and often fail to engraft or remain viable, only the S2 RM molecules are used. Rebuilding of the extracellular matrix and repair of the dysfunctional proteins in the ALS patient ensues.
文摘After onset of myocardial infarction(MI),the left ventricle(LV) undergoes a continuum of molecular,cellular,and extracellular responses that result in LV wall thinning,dilatation,and dysfunction.These dynamic changes in LV shape,size,and function are termed cardiac remodeling.If the cardiac healing after MI does not proceed properly,it could lead to cardiac rupture or maladaptive cardiac remodeling,such as further LV dilatation and dysfunction,and ultimately death.Although the precise molecular mechanisms in this cardiac healing process have not been fully elucidated,this process is strictly coordinated by the interaction of cells with their surrounding extracellular matrix(ECM) proteins.The components of ECM include basic structural proteins such as collagen,elastin and specialized proteins such as fibronectin,proteoglycans and matricellular proteins.Matricellular proteins are a class of non-structural and secreted proteins that probably exert regulatory functions through direct binding to cell surface receptors,other matrix proteins,and soluble extracellular factors such as growth factors and cytokines.This small group of proteins,which includesosteopontin,thrombospondin-1/2,tenascin,periostin,and secreted protein,acidic and rich in cysteine,shows a low level of expression in normal adult tissue,but is markedly upregulated during wound healing and tissue remodeling,including MI.In this review,we focus on the regulatory functions of matricellular proteins during cardiac tissue healing and remodeling after MI.
