In contrast to prevailing dogma, we report that procollagen 1 assembles into a liquid condensate within cells, resolving the long-standing problem of how c

A high-throughput assay using immunoaffinity enrichment coupled to ultra-high-performance liquid chromatography–tandem mass spectrometry for P-III-NP and other fragments of type III procollagen in hu...

In contrast to prevailing dogma, we report that procollagen 1 assembles into a liquid condensate within cells, resolving the long-standing problem of how c

The Institute’s Professor Richard Harvey co-authors study that uncovers a new player in the complex process of heart formation - procollagen IIA.

The selective turnover of endoplasmic reticulum via autophagy (ER-phagy) is a fundamentally important pathway that is activated under different stresses to remove misfolded ER proteins or excess ER to...

This study reveals the structural basis of collagen processing by the KOGG complex, revealing how it catalyzes lysine hydroxylation and dual-glycosylation, essential for collagen folding and stability...

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial disease that develops in several clinical settings. Despite its complex pathogenesis, evidence indicates a central role for fibrosis in the progression of left ventricular diastolic dysfunction (LVDD). Through exploratory research into adipokines derived from brown adipose tissue (BAT), we identified a secreted-type profibrotic protein, procollagen C-endopeptidase enhancer-1 (PCPE-1), whose expression increased in BAT with aging. PCPE-1 promotes the cleavage of procollagens and is a critical initiator of fibrillogenesis. This molecule was increased in the plasma of aged mice. In addition to aging, obesity led to an increase in PCPE-1 expression in the LV of mice. Both systemic and BAT-specific PCPE-1 depletion ameliorated LV fibrosis and LVDD in the obese HFpEF model. Our data also showed that age-associated LVDD was ameliorated in the systemic PCPE-1–KO mouse fed with a normal chow diet. Conversely, the overexpression of PCPE-1 expression in BAT was shown to lead to aggravation of LV fibrosis and LVDD. Mechanistically, we found ROS/DNA damage/c-Fos/c-Jun signaling resulted in an increased production of PCPE-1 in brown adipocytes. These results indicate PCPE-1 may represent a druggable target for aging- and obesity-related HFpEF.

In contrast to prevailing dogma, we report that procollagen 1 assembles into a liquid condensate within cells, resolving the long-standing problem of how c

This secondary analysis of the Randomized Trial to Prevent Vascular Events in HIV (REPREIVE) randomized clinical trial investigates the associations of statin therapy with protein and gene pathways in...