Functional characterization of a putative serine carboxypeptidase in vascular smooth muscle cells.

Content Provider	Semantic Scholar
Author	Lee, Ting-Hein D. Chen, Jiyuan Miano, Joseph M.
Copyright Year	2009
Abstract	RATIONALE We previously identified a novel serine carboxypeptidase, SCPEP1, that undergoes cleavage across all tissues where it is expressed. SCPEP1 bears the signature catalytic triad found in all serine carboxypeptidases, but its biological function is completely unknown. OBJECTIVE To begin elucidating the functions of SCPEP1 in vitro and in the vessel wall after injury. METHODS AND RESULTS Cultured smooth muscle cells were transduced with adenovirus carrying wild-type Scpep1, a short hairpin RNA to Scpep1, or variants of Scpep1 with mutations that disrupt the catalytic triad domain or SCPEP1 cleavage. Western blotting of key growth regulators or growth and migratory responses were assessed following SCPEP1 gain- or loss-of-function in smooth muscle cells. Vascular injury-induced remodeling and cell proliferation were evaluated in wild-type or newly created Scpep1 knockout mice. Overexpression of wild-type or cleavage-defective SCPEP1, but not a catalytic triad mutant SCPEP1, promotes smooth muscle cell proliferation and migration in vitro. A short hairpin RNA to Scpep1 blunts endogenous growth, which is rescued on concurrent expression of Scpep1 carrying silent mutations that evade knockdown. SCPEP1 protein is highly expressed in the neointima of 2 models of vascular remodeling. Scpep1-null mice show decreases in medial and intimal cell proliferation as well as vessel remodeling following arterial injury. CONCLUSIONS SCPEP1 promotes smooth muscle cell proliferation and migration in a catalytic triad-dependent, cleavage-independent manner. SCPEP1 represents a new mediator of vascular remodeling and a potential therapeutic target for the treatment of vascular occlusive diseases.
Starting Page	377
Ending Page	386
Page Count	10
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://circres.ahajournals.org/content/circresaha/105/3/271.full.pdf
Alternate Webpage(s)	http://circres.ahajournals.org/content/circresaha/early/2009/07/02/CIRCRESAHA.109.199869.full.pdf
PubMed reference number	19574551v1
Alternate Webpage(s)	https://doi.org/10.1161/CIRCRESAHA.109.199869
DOI	10.1161/circresaha.109.199869
Journal	Circulation research
Volume Number	105
Issue Number	3
Language	English
Access Restriction	Open
Subject Keyword	Body tissue Cell Proliferation Cerebrovascular Disorders In Vitro [Publication Type] Mediator brand of benfluorex hydrochloride Muscle Cells Muscle, Smooth, Vascular Myocytes, Smooth Muscle Peripheral Vascular Diseases SCPEP1 gene Short Hairpin RNA Silent Mutation Smooth muscle (tissue) Ursidae Family Vascular Remodeling Western Blotting serine-type D-Ala-D-Ala carboxypeptidase
Content Type	Text
Resource Type	Article