Dermatology- a sign of a systemic disease

Intro

Skin manifestations often reflect underlying systemic pathology and provide important insights into disease mechanisms. This session will explore whether tissue turnover is linked to ECM quality and identify key aspects of skin biology that need to be addressed to improve patients’ lives.

Insights into ECM remodeling in skin aging and disease

Andrea Heinz, Associate Professor at the Department of Pharmacy, University of Copenhagen.

Abstract: Extracellular matrix (ECM) remodeling plays a central role in both skin aging and inflammatory disease, yet the time course and mechanisms through which these changes unfold remain incompletely understood. This presentation will explore how structural protein vulnerability, protease activity, and external stressors interact to shape ECM integrity, focusing on how these processes can be monitored at the molecular level using ex vivo human and animal skin.

Using human skin samples spanning different ages and lifetime sun exposure, we examined how elastin morphology evolves and how these changes influence enzymatic susceptibility. Scanning electron microscopy combined with LC‑MS/MS after controlled proteolysis revealed that elastin becomes progressively roughened and fragmented with age and UV exposure. These alterations increase its vulnerability to cleavage, producing distinct peptide release patterns particularly in hydrophobic tropoelastin regions. The shift becomes especially marked in individuals above ~70 years, highlighting elastin as a long‑lived molecule that gradually accumulates damage.

To understand how inflammation reshapes the ECM, we applied targeted PRM proteomics to an imiquimod‑induced psoriasis‑like mouse model. Here, MMP networks were dramatically reorganized: MMP‑2, ‑7, ‑8, and ‑13 increased substantially, while MMP‑3, ‑9, and ‑10 appeared exclusively in inflamed tissue. MMP‑7 consistently dominated in abundance, and several proteases rose dynamically over time, indicating a broadened proteolytic environment resembling human psoriatic lesions.

Finally, in a UV‑exposure mouse model analyzed using DIA‑PASEF mass spectrometry, we assessed how photodamage affects ECM proteins and whether interventions such as ablative laser treatment or nicotinamide could modulate early molecular changes. While the two treatments did not differ from each other in their molecular effects, UV‑exposed groups differed clearly from untreated controls, reinforcing that even early UV‑driven disruptions are detectable at the proteomic level.

Together, these studies illustrate ECM remodeling as a unifying thread across intrinsic aging, photoaging, and inflammation. By combining structural assessment with quantitative proteomics, we can identify early molecular indicators of tissue stress and begin to define how future ECM‑targeted interventions might preserve or restore skin integrity..

Title TBD

Christian Vestergaard, Professor of Dermatology at Aarhus University, dermatologist at Aarhus University Hospital

Abstract: TBD