ArticleProceedings of the National Academy of Sciences of the United States of America2014
Biological role of prolyl 3-hydroxylation in type IV collagen.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
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- Platelet-Collagen Interactions in Hemostatic Mechanisms.Advanced healthcare materials · 2026Review
- Prolyl-3-hydroxylase 1 is a central regulator of collagen post-translational modifications and the collagen biosynthetic network.The Journal of biological chemistry · 2026Article
- Targeting Prolyl 3-hydroxylase 1 inhibits pancreatic cancer progression and macrophage immunity.Nature communications · 2026Article
- Prolyl 3-Hydroxylase 2 Supports a Pro-Angiogenic Milieu Promoting Colorectal Cancer Progression and Metastasis.International journal of molecular sciences · 2026Article
- Evidence for the major role of PH4⍺EFB in the prolyl 4-hydroxylation of Drosophila collagen IV.Matrix biology : journal of the International Society for Matrix Biology · 2025Article
- Collagen IV biosynthesis: Intracellular choreography of post-translational modifications.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- The life cycle of type IV collagen.Matrix biology : journal of the International Society for Matrix Biology · 2025Review
- Beyond classical collagen: basement membrane collagen IV in age-associated lung diseases.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- A multifunction murine Col4a1 allele reveals potential gene therapy parameters for Gould syndrome.The Journal of cell biology · 2025Article
- Mass spectrometry reveals age-dependent collagen decline in murine atria.Annals of the New York Academy of Sciences · 2025Article
- Article
- Comprehensive analysis of the effects ofFrontiers in cell and developmental biology · 2025Article
- The structural basis for the collagen processing by human P3H1/CRTAP/PPIB ternary complex.Nature communications · 2024Article
- Role of ZNF334 in cervical cancer: implications for EMT reversal and tumor suppression.Medical oncology (Northwood, London, England) · 2024Article
- The Versatility of Collagen in Pharmacology: Targeting Collagen, Targeting with Collagen.International journal of molecular sciences · 2024Review
- ColPTMScape: An open access knowledge base for tissue-specific collagen PTM maps.Matrix biology plus · 2024Article
- Construction of an Exudative Age-Related Macular Degeneration Diagnostic and Therapeutic Molecular Network Using Multi-Layer Network Analysis, a Fuzzy Logic Model, and Deep Learning Techniques: Are Retinal and Brain Neurodegenerative Disorders Related?Pharmaceuticals (Basel, Switzerland) · 2023Article
- Collagen Type II-Chitosan Interactions as Dependent on Hydroxylation and Acetylation Inferred from Molecular Dynamics Simulations.Molecules (Basel, Switzerland) · 2022Article
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Collagens constitute nearly 30% of all proteins in our body. Type IV collagen is a major and crucial component of basement membranes. Collagen chains undergo several posttranslational modifications that are indispensable for proper collagen function. One of these modifications, prolyl 3-hydroxylation, is accomplished by a family of prolyl 3-hydroxylases (P3H1, P3H2, and P3H3). The present study shows that P3H2-null mice are embryonic-lethal by embryonic day 8.5. The mechanism of the unexpectedly early lethality involves the interaction of non-3-hydroxylated embryonic type IV collagen with the maternal platelet-specific glycoprotein VI (GPVI). This interaction results in maternal platelet aggregation, thrombosis of the maternal blood, and death of the embryo. The phenotype is completely rescued by producing double KOs of P3H2 and GPVI. Double nulls are viable and fertile. Under normal conditions, subendothelial collagens bear the GPVI-binding sites that initiate platelet aggregation upon blood exposure during injuries. In type IV collagen, these sites are normally 3-hydroxylated. Thus, prolyl 3-hydroxylation of type IV collagen has an important function preventing maternal platelet aggregation in response to the early developing embryo. A unique link between blood coagulation and the ECM is established. The newly described mechanism may elucidate some unexplained fetal losses in humans, where thrombosis is often observed at the maternal/fetal interface. Moreover, epigenetic silencing of P3H2 in breast cancers implies that the interaction between GPVI and non-3-hydroxylated type IV collagen might also play a role in the progression of malignant tumors and metastasis.
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