Global Fibrosis Burden and a Transcriptional Biomarker-Based Strategy for Early Detection in Resource-Limited Settings.

Fibrotic diseases contribute to nearly half of all deaths in industrialized countries, yet effective early detection strategies remain lacking, particularly in low-resource settings. This study aimed to quantify the global burden of fibrosis-related diseases using updated global burden of disease (GBD) 2021 data across 204 countries and territories and establish a cost-effective diagnostic approach targeting vestigial-like family member 3 (VGLL3), a fibrosis-associated transcriptional co-regulator. Our analysis revealed that from 1990 to 2021, fibrosis-related disability-adjusted life years (DALYs) and mortality increased by 16.71% and 4.83%, respectively, with neoplasms and chronic obstructive pulmonary disease (COPD) being the main contributors. We also found a growing burden disproportionately concentrated in low socio-demographic index (SDI) regions. To address the diagnostic gap, we developed a novel immunoassay targeting VGLL3, an intrinsically disordered transcriptional co-regulator implicated in early fibrotic remodeling. The assay demonstrated a detection range of 27.01-2512.36 nM and a limit of detection of 12.55 nM. Immunohistochemical validation in a mouse myocardial infarction model confirmed the antibody's specificity in fibrotic tissues. This work highlights widening global health disparities in fibrosis burden and introduces a cost-effective, scalable diagnostic strategy for early fibrosis detection, particularly suitable for resource-limited settings.