GeneTex
Mosaic Progerin Expression and Early Vascular Aging in Chronic Kidney Disease
 |
Early vascular aging (EVA), a key feature of chronic kidney disease (CKD), is characterized by arterial stiffening, calcification, vascular smooth muscle cell (VSMC) loss, and endothelial dysfunction. The resulting compromised renal function that defines CKD elevates the risk of cardiovascular disease (CVD). Given the connection between EVA, CKD, and CVD that extends beyond traditional CVD risk factors, the identification of additional CVD-predictive biomarkers in the context of EVA and CKD is crucial for the development of new targeted therapies.
In a recent study in Nature Aging, Revêchon et al. elucidate a novel mechanism contributing to EVA in CKD (1). The authors report recurrent somatic expression of progerin, a truncated lamin A isoform causative in Hutchinson–Gilford progeria syndrome (HGPS), in VSMCs of CKD arteries. Remarkably, the classic HGPS mutation LMNA c.1824C>T was identified as a somatic variant in 78.3% of CKD artery samples. These progerin-positive VSMCs demonstrated clonal expansion and were associated with enhanced DNA damage response activation, endoplasmic reticulum stress, and cellular senescence. Using inducible lineage-tracing mouse models harboring the LMNA mutation, the study confirmed that progerin-expressing VSMCs clonally propagate and induce EVA-like phenotypes in vivo, including VSMC loss, medial fibrosis, and upregulation of osteogenic genes.
This study provides compelling evidence that a recurrent somatic mutation in a known mutational hotspot can contribute to EVA in CKD, and emphasizes the importance of somatic genetic variation analysis in revealing previously unknown contributors to diseases of widespread significance.
GeneTex’s well-cited ATR (phospho Thr1989) antibody (GTX128145) was used for IHC as a marker of ongoing DNA damage in both in vitro and ex vivo CKD vascular samples in this study. GeneTex offers an outstanding catalog of antibodies for cell biology research. To learn more, please visit the GeneTex website.
Featured Products
|
|
|
|
||||||||||||||||
Reference:
| (1) Nat Aging. 2025 Jun;5(6):1046-1062. doi: 10.1038/s43587-025-00882-6. |