ArticleHuman molecular genetics2013
Armet/Manf and Creld2 are components of a specialized ER stress response provoked by inappropriate formation of disulphide bonds: implications for genetic skeletal diseases.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Integrative omics profiling of CRELD2 in ccRCC: a nexus of genetics, prognosis, and tumor microenvironment.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Endoplasmic Reticulum Redoxome: Protein Folding and Beyond.Biochemistry · 2026Review
- ElevatedInternational journal of molecular sciences · 2025Article
- Construction of a Novel Secreted Protein Database and Identification of a New Adipokine CRELD2.Diabetes & metabolism journal · 2025Article
- The role of the unfolded protein response pathway in bone homeostasis and potential therapeutic target in cancer-associated bone disease.Bone research · 2025Review
- Endothelial cell-secreted bone targeting exosomes promote angiogenesis coupling with osteogenesis via the PERK-ATF4-CRELD2 pathway.Stem cell research & therapy · 2025Article
- BiallelicBrain communications · 2025Article
- RNASeq highlights ATF6 pathway regulators for CHO cell engineering with different impacts of ATF6β and WFS1 knockdown on fed-batch production of IgGScientific reports · 2024Article
- Molecular characterization of the ER stress-inducible factor CRELD2.Cell biochemistry and biophysics · 2024Article
- Article
- Cysteine-rich with EGF-like domains 2 (CRELD2) is an endoplasmic reticulum stress-inducible angiogenic growth factor promoting ischemic heart repair.Nature cardiovascular research · 2024Article
- Upregulation of mesencephalic astrocyte-derived neurotrophic factor (MANF) expression offers protection against alcohol neurotoxicity.Journal of neurochemistry · 2023Article
- Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal tissue transcriptome of gilts.BMC genomics · 2023Article
- Curcumin Reduces Pathological Endoplasmic Reticulum Stress through Increasing Proteolysis of Mutant Matrilin-3.International journal of molecular sciences · 2023Article
- CDNF and MANF in the brain dopamine system and their potential as treatment for Parkinson's disease.Frontiers in psychiatry · 2023Review
- CRELD2, endoplasmic reticulum stress, and human diseases.Frontiers in endocrinology · 2023Review
- CDNF Interacts with ER Chaperones and Requires UPR Sensors to Promote Neuronal Survival.International journal of molecular sciences · 2022Article
- CRELD2 is a novel modulator of calcium release and calcineurin-NFAT signalling during osteoclast differentiation.Scientific reports · 2022Article
- Cerebral dopamine neurotrophic factor protects and repairs dopamine neurons by novel mechanism.Molecular psychiatry · 2022Review
- Creld2 function during unfolded protein response is essential for liver metabolism homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Mutant matrilin-3 (V194D) forms non-native disulphide bonded aggregates in the rER of chondrocytes from cell and mouse models of multiple epiphyseal dysplasia (MED). Intracellular retention of mutant matrilin-3 causes endoplasmic reticulum (ER) stress and induces an unfolded protein response (UPR) including the upregulation of two genes recently implicated in ER stress: Armet and Creld2. Nothing is known about the role of Armet and Creld2 in human genetic diseases. In this study, we used a variety of cell and mouse models of chondrodysplasia to determine the genotype-specific expression profiles of Armet and Creld2. We also studied their interactions with various mutant proteins and investigated their potential roles as protein disulphide isomerases (PDIs). Armet and Creld2 were up-regulated in cell and/or mouse models of chondrodysplasias caused by mutations in Matn3 and Col10a1, but not Comp. Intriguingly, both Armet and Creld2 were also secreted into the ECM of these disease models following ER stress. Armet and Creld2 interacted with mutant matrilin-3, but not with COMP, thereby validating the genotype-specific expression. Substrate-trapping experiments confirmed Creld2 processed PDI-like activity, thus identifying a putative functional role. Finally, alanine substitution of the two terminal cysteine residues from the A-domain of V194D matrilin-3 prevented aggregation, promoted mutant protein secretion and reduced the levels of Armet and Creld2 in a cell culture model. We demonstrate that Armet and Creld2 are genotype-specific ER stress response proteins with substrate specificities, and that aggregation of mutant matrilin-3 is a key disease trigger in MED that could be exploited as a potential therapeutic target.
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