Biology subjects

Karsdal, M.

Publications and source records attributed to Karsdal, M..

3 recordsLinked to original sources

bioRxiv2026

Multimodal profiling establishes ovarian fibrosis as a measurable and targetable hallmark of human reproductive aging

ABSTRACT Ovarian aging underpins infertility, systemic morbidity, and mortality in women. Stromal fibrosis is implicated in ovarian aging but has not been defined in the human ovary in situ. We integrated shear wave elastography (SWE), extracellular matrix (ECM) neoepitope fingerprinting, and singlecell RNA sequencing of follicular fluid aspirates within the same individual to comprehensively profile ovarian fibrosis. In an age-stratified cohort (<33 and >37 years; N=32), age predicted ovarian stiffness, while mean stiffness was independently associated with reduced oocyte yield and follicular efficiency. ECM profiling revealed a dynamic fibrotic index favoring formation over degradation products. Single-cell transcriptomics demonstrated an age-associated fibroinflammatory stromal program enriched in pro-fibrotic pathways with stromal-immune crosstalk. In a larger validation cohort (25-45 years; N=100), age was similarly associated with ovarian stiffness. Thus, ovarian fibrosis is a quantifiable hallmark of human reproductive aging and represents a robust potential non-invasive biomarker and target for therapeutic intervention.

cell biology↗

bioRxiv2026

Type VI collagen is proportionally lower around airways and blood vessels in idiopathic pulmonary fibrosis

Type VI collagen (COL6) is a key extracellular matrix protein that supports matrix organization and cell-matrix interactions, yet its regulation in idiopathic pulmonary fibrosis (IPF) remains poorly understood. Here, we characterize COL6 gene expression, spatial localization, remodeling, and functional effects of COL6-derived fragments. Analysis of publicly available single-cell RNA sequencing data from 30 controls and 32 pulmonary fibrosis patients revealed higher expression of COL6A1-A6 in fibrotic lungs, predominantly in mesenchymal cells (A1: p=0.0002, A2: p=0.0005, A3: p=2.5x10-5, A5: p=0.016, A6: p=0.007). Immunohistochemical analysis of lung tissue from never-smoker (n=9), ex-smoker (n=9) controls, and IPF patients (n=12) showed extensive COL6 localization across parenchyma, airways, and vessels. The proportion of COL61 and COL62 was lower around IPF vessels (1: p<0.001, 2: p=0.012), and COL62 was lower around IPF airways (p=0.033) compared with never-smokers. Quantification of COL6 remodeling fragments in lung tissue from never-smoker (n=3), ex-smoker (n=5) controls, and IPF patients (n=10) revealed that COL6 production (PRO-C6) localized around airways and vessels but was proportionally lower in IPF airways (never-smokers: p=0.0075). In contrast, COL6 degradation (C6M) was widely distributed throughout the tissue, with lower levels in IPF (never-smokers: p=0.0008). Functionally, COL6 and PRO-C6 increased fibroblast viability (COL6: p=0.002, PRO-C6: p=0.0021), while apoptosis was unaffected. Similar trends were observed in epithelial and endothelial cells. In summary, despite increased COL6 gene expression, IPF lungs exhibited lower proportions of COL6 protein and synthesis around airways and vessels, suggesting disrupted matrix organization, altered remodeling, and pro-survival effects that may contribute to fibroblast persistence and fibrosis progression. New & NoteworthyIn this study, we revealed that IPF lungs are characterized by increased type VI collagen (COL6) gene expression but lower COL6 protein and turnover proportions around airways and blood vessels compared with controls. COL6 and a fragment associated with its production (PRO-C6) increased lung fibroblast viability. These findings highlight that pulmonary fibrotic tissue is characterized by disrupted extracellular matrix and altered tissue remodeling and suggest that COL6 may contribute to fibroblast persistence and fibrosis progression.

molecular biology↗

bioRxiv2024

Identification of novel plasma proteomic biomarkers of Dupuytren Disease

Dupuytren Disease (DD) is a chronic progressive disease that can cause disabling hand deformities. The most common treatments have either high complication rates or high early recurrence rates. Dupuytren lacks a staging biomarker profile to inform the development of preventive therapeutics to improve long-term outcomes. This multi-omic study aimed to create a DD blood proteomic biomarker profile by comparing DD plasma with that of a healthy control group. We measured circulating collagen metabolism peptides and found normal Collagen I synthesis but impaired Collagen I degradation in DD. We measured 6995 serum protein aptamers and identified 68 proteins that showed statistically significant differences compared with the control group. We developed two Diagnostic Proteomic Risk Scores (DPRS) based on hypothesis-free and hypothesis-based analyses. In independent data, our hypothesis-free and hypothesis-based DPRS distinguished Dupuytren from control subjects with accuracies of 76.5% and 70.6%, respectively. Our hypothesis-based DPRS also distinguished DD subjects with different disease progression rates by age at their first corrective procedure (p=0.0018). This pilot study is the first to provide evidence to suggest that Collagen I accumulation in DD results from impaired degradation rather than increased collagen synthesis. It also describes novel DPRS that have potential use as diagnostic and staging biomarker panels for Dupuytren disease.

molecular biology↗