LIM and cysteine-rich domains 1 is required for thrombininduced smooth muscle cell proliferation and promotes atherogenesis

Jagadeesh Janjanam, Baolin Zhang, Arul M. Mani, Nikhlesh Singh, James G. Traylor, A. Wayne Orr, Rao Gadiparthi

Research output: Contribution to journalArticle

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Abstract

Restenosis arises after vascular injury and is characterized by arterial wall thickening and decreased arterial lumen space. Vascular injury induces the production of thrombin, which in addition to its role in blood clotting acts as a mitogenic and chemotactic factor. In exploring the molecular mechanisms underlying restenosis, here we identified LMCD1 (LIM and cysteine- rich domains 1) as a gene highly responsive to thrombin in human aortic smooth muscle cells (HASMCs). Of note, LMCD1 depletion inhibited proliferation of human but not murine vascular smooth muscle cells. We also found that by physically interacting with E2F transcription factor 1, LMCD1 mediates thrombin-induced expression of theCDC6(cell division cycle 6) gene in the stimulation of HASMC proliferation. Thrombin-induced LMCD1 and CDC6 expression exhibited a requirement for protease-activated receptor 1-mediated Gαq/11-dependent activation of phospholipase C β3. Moreover, the expression of LMCD1 was highly induced in smooth muscle cells located at human atherosclerotic lesions and correlated with CDC6 expression and that of the proliferation marker Ki67. Furthermore, the LMCD1- and SMCαactin-positive cells had higher cholesterol levels in the atherosclerotic lesions. In conclusion, these findings indicate that by acting as a co-activator with E2F transcription factor 1 in CDC6 expression, LMCD1 stimulates HASMC proliferation and thereby promotes human atherogenesis, suggesting an involvement of LMCD1 in restenosis.

Original languageEnglish (US)
Pages (from-to)3088-3103
Number of pages16
JournalJournal of Biological Chemistry
Volume293
Issue number9
DOIs
StatePublished - Jan 1 2018

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Cell proliferation
Smooth Muscle Myocytes
Cysteine
Muscle
Atherosclerosis
Cell Proliferation
Thrombin
Cells
E2F1 Transcription Factor
Vascular System Injuries
Genes
PAR-1 Receptor
cdc Genes
Chemotactic Factors
Type C Phospholipases
Blood Coagulation
Hypercholesterolemia
Vascular Smooth Muscle
Blood
Chemical activation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

LIM and cysteine-rich domains 1 is required for thrombininduced smooth muscle cell proliferation and promotes atherogenesis. / Janjanam, Jagadeesh; Zhang, Baolin; Mani, Arul M.; Singh, Nikhlesh; Traylor, James G.; Orr, A. Wayne; Gadiparthi, Rao.

In: Journal of Biological Chemistry, Vol. 293, No. 9, 01.01.2018, p. 3088-3103.

Research output: Contribution to journalArticle

Janjanam, Jagadeesh ; Zhang, Baolin ; Mani, Arul M. ; Singh, Nikhlesh ; Traylor, James G. ; Orr, A. Wayne ; Gadiparthi, Rao. / LIM and cysteine-rich domains 1 is required for thrombininduced smooth muscle cell proliferation and promotes atherogenesis. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 9. pp. 3088-3103.
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