AIMP3 induces laminopathy and senescence of vascular smooth muscle cells by reducing lamin A expression and leads to vascular aging in vivo.

Abstract

Aminoacyl-tRNA synthetase-interacting multifunctional protein 3 (AIMP3), a tumor suppressor, mediates a progeroid phenotype in mice by downregulating lamin A. We investigated whether AIMP3 induces laminopathy and senescence of human aortic smooth muscle cells (HASMCs) and is associated with vascular aging in mice and humans in line with decreased lamin A expression. Cellular senescence was evaluated after transfecting HASMCs with AIMP3. Molecular analyses of genes encoding AIMP3, lamin A, chemokine (C-C motif) ligand 2 (CCL2), and C-C chemokine receptor type 2 (CCR2) and histological comparisons of aortas were performed with mice at various ages (7 weeks, 5 months, 12 months, 24 months, and 32 months), AIMP3-transgenic mice, and human femoral arteries of cadavers. AIMP3-transfected HASMCs exhibited increased AIMP3 and senescence marker p16 protein expression and decreased lamin A protein expression in accordance with their disrupted nuclear morphology in histological analyses. AIMP3-transgenic mice displayed increased AIMP3 protein expression and decreased lamin A protein expression in aortas together with typical aging pathologies. Similar changes were observed in wild-type aging (24-month-old) mice but not in wild-type young (7-week-old) mice. In humans, AIMP3 and lamin A protein expression was higher and lower, respectively, in femoral arteries of elderly individuals than in those of their younger counterparts. This study found that AIMP3 overexpression in vitro decreased lamin A expression and induced nuclear laminopathy and cellular senescence. Similar findings were made in the vasculature of aging mice and elderly humans.

• Authors: Byung Hee Hwang, Eunmin Kim, Eun-Hye Park, Chan Woo Kim, Kwan-Yong Lee, Jin-Jin Kim, Eun Ho Choo, Sungmin Lim, Ik Jun Choi, Chan Joon Kim, Sang-Hyun Ihm, Kiyuk Chang
• Journal: Experimental gerontology (Exp Gerontol) Vol. 153 Pg. 111483 (10 01 2021) ISSN: 1873-6815 [Electronic] England
• PMID: 34274427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Lamin Type A

Topics

• Aging
• Animals
• Cells, Cultured
• Cellular Senescence
• Lamin Type A (genetics)
• Laminopathies
• Mice
• Muscle, Smooth, Vascular
• Myocytes, Smooth Muscle