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Article ; Online: Epididymal DIS3 exosome ribonuclease is not necessary for mouse sperm maturation or fertility.

Qiu, Fanyi / Wang, Xiao / Zhou, Meiyang / Yu, Junjie / Wang, Zhengpin

Biochemical and biophysical research communications

2023 Volume 666, Page(s) 36–44

Abstract: DIS3 is an RNA exosome associated ribonuclease that degrades a wide range of transcripts that can be essential for cell survival and development. The proximal region of the mouse epididymis (initial segment and caput) plays a pivotal role in sperm ... ...

Abstract	DIS3 is an RNA exosome associated ribonuclease that degrades a wide range of transcripts that can be essential for cell survival and development. The proximal region of the mouse epididymis (initial segment and caput) plays a pivotal role in sperm transport and maturation required for male fertility. However, whether DIS3 ribonuclease mediates RNA decay in proximal epididymides remains unclear. Herein, we established a conditional knockout mouse line by crossing a floxed Dis3 allele with Lcn9-cre mice in which the recombinase is expressed in the principal cells of initial segment as early as post-natal day 17. Morphological and histological analyses, immunofluorescence, computer-aided sperm analysis and fertility were used for functional analyses. We document that DIS3 deficiency in the initial segment had no effect on male fertility. Dis3 cKO males had normal spermatogenesis and initial segment development. In cauda epididymides of Dis3 cKO mice, sperm abundance, morphology, motility, and the frequency of acrosome exocytosis were comparable to controls. Collectively, our genetic model demonstrates that loss of DIS3 in the initial segment of the epididymis is not essential for sperm maturation, motility, or male fertility.
MeSH term(s)	Male ; Animals ; Mice ; Epididymis/metabolism ; Sperm Maturation ; Ribonuclease, Pancreatic/metabolism ; Ribonucleases/metabolism ; Exosomes ; Semen ; Spermatozoa/metabolism ; Fertility/genetics ; Mice, Knockout ; Sperm Motility/genetics ; Exosome Multienzyme Ribonuclease Complex/metabolism
Chemical Substances	Ribonuclease, Pancreatic (EC 3.1.27.5) ; Ribonucleases (EC 3.1.-) ; Dis3 protein, mouse (EC 3.1.13-) ; Exosome Multienzyme Ribonuclease Complex (EC 3.1.-)
Language	English
Publishing date	2023-05-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.05.023
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Article ; Online: scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells

Zhengpin Wang / Xiaojiang Xu

Cells, Vol 9, Iss 920, p

2020 Volume 920

Abstract: In December 2019, a novel coronavirus (SARS-CoV-2) was identified in COVID-19 patients in Wuhan, Hubei Province, China. SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), ... ...

Abstract	In December 2019, a novel coronavirus (SARS-CoV-2) was identified in COVID-19 patients in Wuhan, Hubei Province, China. SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes of SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not yet been determined. Here, we investigate the expression pattern of ACE2 in adult human testes at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia and Leydig and Sertoli cells. Gene Set Enrichment Analysis (GSEA) indicates that Gene Ontology (GO) categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia, while male gamete generation related terms are downregulated. Cell–cell junction and immunity-related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction-related GO terms are decreased. These findings provide evidence that the human testis is a potential target of SARS-CoV-2 infection, which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.
Keywords	SARS-CoV-2 ; infection ; scRNA-seq ; ACE2 ; spermatogonia ; Biology (General) ; QH301-705.5 ; covid19
Subject code	572
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Book ; Online: scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells

Zhengpin Wang / Xiaojiang Xu

Cells ; Volume 9 ; Issue 4

2020

Abstract	In December 2019, a novel coronavirus (SARS-CoV-2) was identified in COVID-19 patients in Wuhan, Hubei Province, China. SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes of SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not yet been determined. Here, we investigate the expression pattern of ACE2 in adult human testes at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia and Leydig and Sertoli cells. Gene Set Enrichment Analysis (GSEA) indicates that Gene Ontology (GO) categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia, while male gamete generation related terms are downregulated. Cell– cell junction and immunity-related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction-related GO terms are decreased. These findings provide evidence that the human testis is a potential target of SARS-CoV-2 infection, which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.
Keywords	SARS-CoV-2 ; infection ; scRNA-seq ; ACE2 ; spermatogonia ; covid19
Subject code	572
Language	English
Publishing date	2020-04-09
Publisher	Multidisciplinary Digital Publishing Institute
Publishing country	ch
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: MAGE-B4, a binding partner of PRAMEF12, is dispensable for spermatogenesis and male fertility in mice.

Li, Nana / Yu, Junjie / Zhou, Meiyang / Qiu, Fanyi / Wang, Xiao / Wang, Zhengpin

Biochemical and biophysical research communications

2023 Volume 675, Page(s) 46–53

Abstract: Melanoma antigen (MAGE)-B4 belongs to the MAGE-B family genes, which are located on the X chromosome. The MAGE-B family genes are classified as cancer-testis antigens, as they are primarily expressed in the testis and are aberrantly expressed in most ... ...

Abstract	Melanoma antigen (MAGE)-B4 belongs to the MAGE-B family genes, which are located on the X chromosome. The MAGE-B family genes are classified as cancer-testis antigens, as they are primarily expressed in the testis and are aberrantly expressed in most cancers. Although a no-stop mutation in MAGE-B4 causes rare X-linked azoospermia and oligozoospermia phenotype in humans, the specific function of MAGE-B4 on spermatogenesis in mice remains unclear. In this study, we identified MAGE-B4 as a binding partner of PRAME family member 12, which plays an important role in the maintenance of mouse spermatogenic lineage in juvenile testes. Additionally, we found that Mage-b4 transcripts were restricted to the testis and that Mage-b4 was specifically expressed in spermatogonia. To explore the function of MAGE-B4 in spermatogenesis, we generated a Mage-b4 knockout (KO) mouse model using CRISPR/Cas9 technology. However, we found that Mage-b4 KO males displayed normal testicular morphology and fertility. Further histological analysis revealed that all stages of spermatogenic cells were present in the seminiferous tubules of the Mage-b4 KO mice. Altogether, our data suggest that Mage-b4 is dispensable for mouse spermatogenesis and male fertility.
MeSH term(s)	Animals ; Male ; Mice ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/metabolism ; Fertility/genetics ; Melanoma/metabolism ; Mice, Knockout ; Spermatogenesis/genetics ; Spermatogonia/metabolism ; Testis/metabolism
Chemical Substances	Antigens, Neoplasm ; Mageb4 protein, mouse ; Pramef12 protein, mouse
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.07.013
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 116: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: scRNA-seq Profiling of Human Testes Reveals the Presence of the ACE2 Receptor, A Target for SARS-CoV-2 Infection in Spermatogonia, Leydig and Sertoli Cells.

Wang, Zhengpin / Xu, Xiaojiang

Cells

2020 Volume 9, Issue 4

Abstract	In December 2019, a novel coronavirus (SARS-CoV-2) was identified in COVID-19 patients in Wuhan, Hubei Province, China. SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes of SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not yet been determined. Here, we investigate the expression pattern of ACE2 in adult human testes at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia and Leydig and Sertoli cells. Gene Set Enrichment Analysis (GSEA) indicates that Gene Ontology (GO) categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia, while male gamete generation related terms are downregulated. Cell-cell junction and immunity-related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction-related GO terms are decreased. These findings provide evidence that the human testis is a potential target of SARS-CoV-2 infection, which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; COVID-19 ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Gene Expression Profiling ; Gene Expression Regulation ; Humans ; Male ; Pandemics ; Peptidyl-Dipeptidase A/genetics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/transmission ; Pneumonia, Viral/virology ; RNA, Small Cytoplasmic/chemistry ; RNA, Small Cytoplasmic/genetics ; Receptors, Virus/genetics ; Receptors, Virus/metabolism ; Testis/cytology ; Testis/metabolism ; Testis/virology ; Virus Replication/genetics
Chemical Substances	RNA, Small Cytoplasmic ; Receptors, Virus ; Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-04-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9040920
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Article ; Online: Epididymal DIS3 exosome ribonuclease is not necessary for mouse sperm maturation or fertility

Qiu, Fanyi / Wang, Xiao / Zhou, Meiyang / Yu, Junjie / Wang, Zhengpin

Biochemical and Biophysical Research Communications. 2023 July, v. 666 p.36-44

2023

Abstract	DIS3 is an RNA exosome associated ribonuclease that degrades a wide range of transcripts that can be essential for cell survival and development. The proximal region of the mouse epididymis (initial segment and caput) plays a pivotal role in sperm transport and maturation required for male fertility. However, whether DIS3 ribonuclease mediates RNA decay in proximal epididymides remains unclear. Herein, we established a conditional knockout mouse line by crossing a floxed Dis3 allele with Lcn9-cre mice in which the recombinase is expressed in the principal cells of initial segment as early as post-natal day 17. Morphological and histological analyses, immunofluorescence, computer-aided sperm analysis and fertility were used for functional analyses. We document that DIS3 deficiency in the initial segment had no effect on male fertility. Dis3 cKO males had normal spermatogenesis and initial segment development. In cauda epididymides of Dis3 cKO mice, sperm abundance, morphology, motility, and the frequency of acrosome exocytosis were comparable to controls. Collectively, our genetic model demonstrates that loss of DIS3 in the initial segment of the epididymis is not essential for sperm maturation, motility, or male fertility.
Keywords	RNA ; acrosome ; alleles ; cell viability ; epididymis ; exocytosis ; exosomes ; fluorescent antibody technique ; genetic models ; histology ; knockout mutants ; male fertility ; mice ; recombinases ; research ; ribonucleases ; sperm transport ; spermatogenesis ; DIS3 ; Mouse epididymis ; Initial segment ; Sperm maturation
Language	English
Dates of publication	2023-07
Size	p. 36-44.
Publishing place	Elsevier Inc.
Document type	Article ; Online
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.05.023
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 71/706: Show issues
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Article ; Online: MAGE-B4, a binding partner of PRAMEF12, is dispensable for spermatogenesis and male fertility in mice

Li, Nana / Yu, Junjie / Zhou, Meiyang / Qiu, Fanyi / Wang, Xiao / Wang, Zhengpin

Biochemical and Biophysical Research Communications. 2023 July 10,

2023

Abstract	Melanoma antigen (MAGE)-B4 belongs to the MAGE-B family genes, which are located on the X chromosome. The MAGE-B family genes are classified as cancer-testis antigens, as they are primarily expressed in the testis and are aberrantly expressed in most cancers. Although a no-stop mutation in MAGE-B4 causes rare X-linked azoospermia and oligozoospermia phenotype in humans, the specific function of MAGE-B4 on spermatogenesis in mice remains unclear. In this study, we identified MAGE-B4 as a binding partner of PRAME family member 12, which plays an important role in the maintenance of mouse spermatogenic lineage in juvenile testes. Additionally, we found that Mage-b4 transcripts were restricted to the testis and that Mage-b4 was specifically expressed in spermatogonia. To explore the function of MAGE-B4 in spermatogenesis, we generated a Mage-b4 knockout (KO) mouse model using CRISPR/Cas9 technology. However, we found that Mage-b4 KO males displayed normal testicular morphology and fertility. Further histological analysis revealed that all stages of spermatogenic cells were present in the seminiferous tubules of the Mage-b4 KO mice. Altogether, our data suggest that Mage-b4 is dispensable for mouse spermatogenesis and male fertility.
Keywords	CRISPR-Cas systems ; chromosomes ; histology ; juveniles ; male fertility ; melanoma-specific antigens ; mice ; mutation ; phenotype ; research ; spermatogenesis ; spermatogonia ; testes ; Melanoma antigen (MAGE)-B4 ; PRAME family member 12 (PRAMEF12) ; CRISPR/Cas9 ; Testis
Language	English
Dates of publication	2023-0710
Size	p. 46-53.
Publishing place	Elsevier Inc.
Document type	Article ; Online
Note	Pre-press version
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2023.07.013
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Bonn / Germany

Z 71/706: Show issues
Z 3.8: Show issues

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Article ; Online: Sperm acrosome overgrowth and infertility in mice lacking chromosome 18 pachytene piRNA.

Choi, Heejin / Wang, Zhengpin / Dean, Jurrien

PLoS genetics

2021 Volume 17, Issue 4, Page(s) e1009485

Abstract: piRNAs are small non-coding RNAs required to maintain genome integrity and preserve RNA homeostasis during male gametogenesis. In murine adult testes, the highest levels of piRNAs are present in the pachytene stage of meiosis, but their mode of action ... ...

Abstract	piRNAs are small non-coding RNAs required to maintain genome integrity and preserve RNA homeostasis during male gametogenesis. In murine adult testes, the highest levels of piRNAs are present in the pachytene stage of meiosis, but their mode of action and function remain incompletely understood. We previously reported that BTBD18 binds to 50 pachytene piRNA-producing loci. Here we show that spermatozoa in gene-edited mice lacking a BTBD18 targeted pachytene piRNA cluster on Chr18 have severe sperm head dysmorphology, poor motility, impaired acrosome exocytosis, zona pellucida penetration and are sterile. The mutant phenotype arises from aberrant formation of proacrosomal vesicles, distortion of the trans-Golgi network, and up-regulation of GOLGA2 transcripts and protein associated with acrosome dysgenesis. Collectively, our findings reveal central role of pachytene piRNAs in controlling spermiogenesis and male fertility.
MeSH term(s)	Acrosome/pathology ; Animals ; Chromosomes/genetics ; Humans ; Infertility, Male/genetics ; Infertility, Male/pathology ; Male ; Meiosis/genetics ; Mice ; Pachytene Stage/genetics ; RNA, Small Interfering/genetics ; Spermatids/growth & development ; Spermatids/pathology ; Spermatogenesis/genetics ; Spermatozoa/pathology ; Testis/growth & development ; Testis/pathology
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2021-04-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1009485
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Transcriptome profiling of the initial segment and proximal caput of mouse epididymis.

Wang, Xiao / Qiu, Fanyi / Yu, Junjie / Zhou, Meiyang / Zuo, Anjian / Xu, Xiaojiang / Sun, Xiao-Yang / Wang, Zhengpin

Frontiers in endocrinology

2023 Volume 14, Page(s) 1190890

Abstract: Background: The proximal region of the mouse epididymis plays a pivotal role in sperm transport, sperm maturation, and male fertility. Several studies have focused on segment-dependent gene expression of the mouse epididymis through high-throughput ... ...

Abstract	Background: The proximal region of the mouse epididymis plays a pivotal role in sperm transport, sperm maturation, and male fertility. Several studies have focused on segment-dependent gene expression of the mouse epididymis through high-throughput sequencing without the precision of the microdissection. Methods and results: Herein, we isolated the initial segment (IS) and proximal caput (P-caput) by physical microdissection using an Conclusion: Thus, this study provides an RNA-seq resource to identify region-specific genes in the caput epididymis. The epididymal-selective/specific genes are potential targets for male contraception and may provide new insights into understanding segment-specific epididymal microenvironment-mediated sperm transport, maturation, and male fertility.
MeSH term(s)	Mice ; Animals ; Male ; Epididymis/metabolism ; Semen ; Sperm Motility ; Gene Expression Profiling ; Spermatozoa/metabolism
Language	English
Publishing date	2023-05-31
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2592084-4
ISSN	1664-2392
ISSN	1664-2392
DOI	10.3389/fendo.2023.1190890
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Article ; Online: USP24-dependent stabilization of Runx2 recruits a p300/NCOA3 complex to transactivate ADAMTS genes and promote degeneration of intervertebral disc in chronic inflammation mice

Xingguo Li / Jun Zhang / Bing Wang / Chao Chen / Enyu Zhang / Zhengpin Lv / Qicong He / Yaoquan Hu / Xuenan Wang / Fan Zhang

Biology Direct, Vol 18, Iss 1, Pp 1-

2023 Volume 14

Abstract: Abstract Background Intervertebral disc degeneration (IDD) naturally occurs during the aging process. Its occurrence is closely related to chronic inflammation; however, the causal relationship between them is controversial. This study aimed to ... ...

Abstract	Abstract Background Intervertebral disc degeneration (IDD) naturally occurs during the aging process. Its occurrence is closely related to chronic inflammation; however, the causal relationship between them is controversial. This study aimed to investigate if inflammation would promote IDD incidence and explore the underlying mechanism. Methods A chronic inflammation mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS). Enzyme-linked immunosorbent assay was performed to determine proinflammatory cytokines in serum. Histological staining was used to evaluate the degeneration of IVDs. Immunoblots and RT-qPCR analyses were performed to measure protein and mRNA expression levels. Immunoprecipitation, mass spectrometry, and co-immunoprecipitation assays were used to determine the assembly of protein complex. Results We found that an inflammatory microenvironment activated p38 kinase, which phosphorylated the Runx2 transcription factor at the Ser28 site. The phosphorylated Runx2 (pRunx2) then recruited a deubiquitinase, ubiquitin-specific peptidase 24 (USP24), which stabilized pRunx2 and protected it from ubiquitin-dependent proteasomal degradation. The stabilized pRunx2 recruited histone acetyltransferase p300 and nuclear receptor coactivator 3 (NCOA3) to assemble a complex. This NCOA3-p300-pRunx2 complex then transactivated the expression of 13 ADAMTS (a disintegrin and metalloproteinase with thrombospondin motif) genes, thereby promoting the degradation of extracellular matrix (ECM) in intervertebral discs (IVDs) and causing IDD. Administration of either a p38 inhibitor (doramapimod), a NCOA3 inhibitor (bufalin), or a p300 inhibitor (EML425) significantly decreased the expression of the 13 ADAMTS genes and slowed the degeneration of IVDs. Conclusion In summary, our results demonstrate that USP24 protects pRunx2 from proteasomal degradation under chronic inflammation conditions, enabling pRunx2 to transactivate ADAMTS genes and degrade ECM. Our findings provide direct evidence that ...
Keywords	USP24 ; ADAMTS ; Runx2 ; p300 ; NCOA3 ; Chronic inflammation ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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