Trial reportProceedings of the National Academy of Sciences of the United States of America2014
CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.
Trial report 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 72 papers.
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The trial behind it
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Who cites it
72 citing papers in PubMed, 108 citations in OpenAlex.
- Genetic Determinants of Microvascular Complications of Type 1 Diabetes Mellitus: New Data from a Replication Study.Biomedicines · 2026Article
- Cathepsin H as a causal risk factor and therapeutic target in proliferative diabetic retinopathy.Journal of translational medicine · 2026Article
- Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon.Cell genomics · 2025Article
- Review
- The Heterogeneity of Type 1 Diabetes: Implications for Pathogenesis, Prevention, and Treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetes care · 2025Review
- Review
- The heterogeneity of type 1 diabetes: implications for pathogenesis, prevention, and treatment-2024 Diabetes, Diabetes Care, and Diabetologia Expert Forum.Diabetologia · 2025Review
- A regulatory variant rs9379874 in T1D risk region 6p22.2 affects BTN3A1 expression regulating T cell function.Acta diabetologica · 2025Article
- Article
- Zebularine showed anti-tumor efficacy in clear cell renal cell carcinoma.Frontiers in pharmacology · 2025Article
- Single-cell and bulk transcriptomic analyses reveal PANoptosis-associated immune dysregulation of fibroblasts in periodontitis.Frontiers in immunology · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Review
- Lysosomal physiology and pancreatic lysosomal stress in diabetes mellitus.eGastroenterology · 2024Article
- Pinpointing Novel Plasma and Brain Proteins for Common Ocular Diseases: A Comprehensive Cross-Omics Integration Analysis.International journal of molecular sciences · 2024Article
- A functional variant rs912304 for late-onset T1D risk contributes to islet dysfunction by regulating proinflammatory cytokine-responsive gene STXBP6 expression.BMC medicine · 2024Article
- Untangling the genetics of beta cell dysfunction and death in type 1 diabetes.Molecular metabolism · 2024Review
- Broadening Horizons: Exploring the Cathepsin Family as Therapeutic Targets for Alzheimer's Disease.Aging and disease · 2024Review
- Integrative multi-omics analysis identifies genetically supported druggable targets and immune cell specificity for myasthenia gravis.Journal of translational medicine · 2024Article
- Genetic and Epigenetic Aspects of Type 1 Diabetes Mellitus: Modern View on the Problem.Biomedicines · 2024Review
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 12 institutions in 6 countries.
Funding
Abstract
Over 40 susceptibility loci have been identified for type 1 diabetes (T1D). Little is known about how these variants modify disease risk and progression. Here, we combined in vitro and in vivo experiments with clinical studies to determine how genetic variation of the candidate gene cathepsin H (CTSH) affects disease mechanisms and progression in T1D. The T allele of rs3825932 was associated with lower CTSH expression in human lymphoblastoid cell lines and pancreatic tissue. Proinflammatory cytokines decreased the expression of CTSH in human islets and primary rat β-cells, and overexpression of CTSH protected insulin-secreting cells against cytokine-induced apoptosis. Mechanistic studies indicated that CTSH exerts its antiapoptotic effects through decreased JNK and p38 signaling and reduced expression of the proapoptotic factors Bim, DP5, and c-Myc. CTSH overexpression also up-regulated Ins2 expression and increased insulin secretion. Additionally, islets from Ctsh(-/-) mice contained less insulin than islets from WT mice. Importantly, the TT genotype was associated with higher daily insulin dose and faster disease progression in newly diagnosed T1D patients, indicating agreement between the experimental and clinical data. In line with these observations, healthy human subjects carrying the T allele have lower β-cell function, which was evaluated by glucose tolerance testing. The data provide strong evidence that CTSH is an important regulator of β-cell function during progression of T1D and reinforce the concept that candidate genes for T1D may affect disease progression by modulating survival and function of pancreatic β-cells, the target cells of the autoimmune assault.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.