Last update 01 Nov 2024

CREG1

Last update 01 Nov 2024

Basic Info

Synonyms

cellular repressor of E1A stimulated genes 1, Cellular repressor of E1A-stimulated genes 1, CREG

+ [2]

Introduction

May contribute to the transcriptional control of cell growth and differentiation. Antagonizes transcriptional activation and cellular transformation by the adenovirus E1A protein. The transcriptional control activity of cell growth requires interaction with IGF2R.

Drugs associated with CREG1

CN117624348

Patent Mining

Target

CREG1

Mechanism-

Active Org.

The General Hospital of Shenyang Military Region

Originator Org.

The General Hospital of Shenyang Military Region [+1]

Active Indication

Cardiovascular Diseases

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CREG1

100 Translational Medicine associated with CREG1

0 Patents (Medical) associated with CREG1

186

Literatures (Medical) associated with CREG1

01 Sep 2024·Redox Biology

CREG1 attenuates doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis of cardiomyocytes

Article

Author: Wu, Hanlin ; Zhang, Xiaolin ; Liu, Dan ; Wang, Jing ; Bu, Yuxin ; Song, Haixu ; Cheng, Xiaoli ; Han, Yaling ; Yan, Chenghui

OBJECTIVEDoxorubicin (DOX)-induced cardiotoxicity limits the application of DOX in cancer patients. Currently, there is no effective prevention or treatment for DOX-induced cardiotoxicity. The cellular repressor of E1A-stimulated genes (CREG1) is a cardioprotective factor that plays an important role in the maintenance of cardiomyocytes differentiation and homeostasis. However, the role and mechanism of CREG1 in DOX-induced cardiotoxicity has not yet been elucidated.METHODSIn vivo, C57BL/6J mice, CREG1 transgenic and cardiac-specific CREG1 knockout mice were used to establish a DOX-induced cardiotoxicity model. H&E staining, Masson's trichrome, WGA staining, real-time PCR, and western blotting were performed to examine fibrosis and ferroptosis in the myocardium. In vitro, neonatal mouse cardiomyocytes (NMCMs) were cultured and stimulated with DOX, CREG1-overexpressed adenovirus, and small interfering RNA was used to establish CREG1 overexpression or knockdown cardiomyocytes. Transcriptomics, real-time PCR, western blotting, and immunoprecipitation were used to examine the roles and mechanisms of CREG1 in cardiomyocytes ferroptosis.RESULTSThe mRNA and protein levels of CREG1 were reduced in the hearts and NMCMs after DOX treatment. CREG1 overexpression alleviated myocardial damage and inhibited DOX-induced ferroptosis in the myocardium. CREG1 deficiency in the heart aggravated DOX-induced cardiotoxicity and ferroptosis. In vitro, CREG1 overexpression inhibited cardiomyocytes ferroptosis induced by DOX, and CREG1 knockdown aggravated DOX-induced cardiotoxicity. Mechanistically, CREG1 inhibited the mRNA and protein expression of pyruvate dehydrogenase kinase 4 (PDK4) by regulating the F-box and WD repeat domain containing 7 (FBXW7)-forkhead box O1 (FOXO1) pathway. PDK4 deficiency reversed the effects of CREG1 knockdown on cardiomyocytes ferroptosis following DOX treatment.CONCLUSIONCREG1 alleviated DOX-induced cardiotoxicity by inhibiting ferroptosis in cardiomyocytes. Our findings may help clarify the new roles of CREG1 in the development of DOX-induced cardiotoxicity.

01 Aug 2024·International Journal of Biological Macromolecules

CREG1 promotes bovine placental trophoblast cells exosome release by targeting IGF2R and participates in regulating organoid differentiation via exosomes transport

Article

Author: Chen, Chang ; Liu, Bingying ; Chen, Jiaxi ; Guo, Kaijun ; Yang, Xiaowen ; Wang, Yingqiu ; Yuan, Naihan ; Ren, Siqi ; Xiao, Longfei ; Yang, Lin ; Wang, Xiangguo ; Qi, Xiaolong ; Sheng, Xihui

BACKGROUNDPlacental exosomes are a kind of intercellular communication media secreted by placental cells during pregnancy, exosomogenesis and release are regulated by many secretory glycoproteins. CREG1 is a kind of secreted glycoprotein widely expressed in various organs and tissues of the body, which inhibits cell proliferation and enhances cell differentiation. The aim of this study was to explore the role of CREG1 in regulating exosomogenesis during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R and participating in regulating organoid differentiation via exosomes transport.METHODSMolecular biological methods were firstly used to investigate the expression patterns of CREG1, IGF2R and exosomal marker proteins in early placental development of pregnant dairy cows. Subsequently, the effects of CREG1 on the formation and release of bovine placental trophoblast (BTCs) derived exosomes by targeting IGF2R were investigated. Further, the effects of CREG1 on the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the differentiation of organoids were explored.RESULTSThe expression of CREG1, IGF2R and exosomal marker proteins increased with the increase of pregnancy months during the early evolution of placental trophoblast cells in dairy cows. Overexpression of Creg1 enhanced the genesis and release of exosomes derived from BTCs, while knocking down the expression of Igf2r gene not only inhibited the genesis of exosomes, but also inhibited the genesis and release of exosomes induced by overexpression of CREG1 protein. Interestingly, IGF2R can regulate the expression of CREG1 through reverse secretion. What's more, the occurrence and release of trophoblast-derived exosomes are regulated by CREG1 binding to IGF2R, which subsequently binds to Rab11. CREG1 can not only promote the formation and release of exosomes in donor cells, but also regulate the change of gene expression patterns along with the transport of exosomes to recipient cells and participate in regulating the early development of placenta.CONCLUSIONSOur study confirmed that CREG1 is involved in the exosomogenesis and release of exosomes during the proliferation and differentiation of placental trophoblast cells in early pregnant dairy cows by targeting IGF2R, and is involved in the regulation of organoid differentiation through exosome transport.

01 Apr 2024·Journal of Cachexia, Sarcopenia and Muscle

CREG1 deficiency impaired myoblast differentiation and skeletal muscle regeneration

Article

Author: Zhou, Ting ; Jia, Xiaodong ; Liu, Dan ; Liu, Chunying ; Han, Yaling ; Yang, Zheming ; Mei, Zhu ; Tian, Xiaoxiang ; Yan, Chenghui ; He, Lianqi ; He, Jiaqi ; Song, Haixu ; Li, Jiayin

AbstractBackgroundCREG1 (cellular repressor of E1A‐stimulated genes 1) is a protein involved in cellular differentiation and homeostasis regulation. However, its role in skeletal muscle satellite cells differentiation and muscle regeneration is poorly understood. This study aimed to investigate the role of CREG1 in myogenesis and muscle regeneration.MethodsRNA sequencing data (GSE8479) was analysed from the Gene Expression Omnibus database (GEO, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi). We generated Creg1 knockdown and skeletal muscle satellite cells specific Creg1 overexpression mice mediated by adeno‐associated virus serotype 9 (AAV9), skeletal muscle mature myofibre Creg1 knockout mice (myoblast/Creg1MKO), and control mice Creg1flox/flox (Creg1fl/fl) as in vivo models. The mice were injected into tibialis anterior (TA) muscle with 100 μL of 10 μM cardiotoxin to establish a muscle regeneration model. Creg1fl/fl and Creg1MKO mice were treated with AAV‐sh‐C‐Cbl (2 × 1010 genomic copies/mouse) to silence C‐Cbl in the TA muscle. 293T and C2C12 cells were transfected with plasmids using lipofectamine RNAi MAX in vitro. Mass spectrometry analyses and RNA sequencing transcriptomic assay were performed.ResultsWe analysed the transcriptional profiles of the skeletal muscle biopsies from healthy older (N = 25) and younger (N = 26) adult men and women in GSE8479 database, and the results showed that Creg1 was associated with human sarcopenia. We found that Creg1 knockdown mice regenerated less newly formed fibres in response to cardiotoxin injection (~30% reduction, P < 0.01); however, muscle satellite cells specific Creg1 overexpression mice regenerated more newly formed fibres (~20% increase, P < 0.05). AMPKa1 is known as a key mediator in the muscle regeneration process. Our results revealed that CREG1 deficiency inhibited AMPKa1 signalling through C‐CBL E3‐ubiquitin ligase‐mediated AMPKa1 degradation (P < 0.01). C‐CBL‐mediated AMPKa1 ubiquitination was attributed to the K48‐linked polyubiquitination of AMPKa1 at K396 and that the modification played an important role in the regulation of AMPKa1 protein stability. We also found that Creg1MKO mice regenerated less newly formed fibres compared with Creg1fl/fl mice (~30% reduction, P < 0.01). RNA‐seq analysis showed that CREG1 deletion in impaired muscles led to the upregulation of inflammation and DKK3 expression. The TA muscles of Creg1MKO mice were injected with AAV‐vector or AAV‐shC‐Cbl, silencing C‐CBL (P < 0.01) in the skeletal muscles of Creg1MKO mice significantly improved muscle regeneration induced by CTX injury (P < 0.01).ConclusionsOur findings suggest that CREG1 may be a potential therapeutic target for skeletal muscle regeneration.

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