Loss of the Serum Response Factor Cofactor, Cysteine-Rich Protein 1, Attenuates Neointima Formation in the Mouse

Lilly, Brenda; Clark, Kathleen; Yoshigi, Masaaki; Pronovost, Stephen M.; Wu, Mingyang; Periasamy, Muthu; Chi, Mei; Rutgeerts, Paul; Yet, Shaw‐Fang; Beckerle, Mary C.

doi:10.1161/atvbaha.109.200741

Cited by 27 publications

(21 citation statements)

References 37 publications

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“…It is interesting to contrast the findings reported here with several other smooth muscle-restricted actin-binding proteins that are dispensable for similar functional activity in these organs, including CNN1 (17,36), TAGLN (37), CSRP1 (38), and CALD1 (39), which would suggest that compensatory pathways exist to preserve normal organ function in the absence of each of these actin-binding proteins. On the other hand, genetic inactivation of Myh11, encoding the major thick filament protein in smooth muscle, leads to megacystis, a decrease in intestinal motility, defective contraction of the bladder, and early postnatal death, all of which are reminiscent of the Lmod1 −/− phenotype and human MMIHS (40).…”

Section: Discussioncontrasting

confidence: 55%

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Halim

Wilson

Oliver

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

108

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Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells. Parents heterozygous for the mutation exhibited no abnormalities, but a child homozygous for the premature termination codon displayed symptoms consistent with MMIHS. We used CRISPR-Cas9 (CRISPR-associated protein) genome editing of Lmod1 to generate a similar premature termination codon. Mice homozygous for the mutation showed loss of LMOD1 protein and pathology consistent with MMIHS, including late gestation expansion of the bladder, hydronephrosis, and rapid demise after parturition. Loss of LMOD1 resulted in a reduction of filamentous actin, elongated cytoskeletal dense bodies, and impaired intestinal smooth muscle contractility. These results define LMOD1 as a disease gene for MMIHS and suggest its role in establishing normal smooth muscle cytoskeletal–contractile coupling.

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Section: Discussioncontrasting

confidence: 55%

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Halim

Wilson

Oliver

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

108

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“…CSRP1 is expressed primarily in VSMCs and in sensing or responding to pathological vascular stress and maintaining smooth muscle homeostasis [33]. It is thought to be critical for smooth muscle differentiation.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Aorta and Protective Effects of Grape Seed Procyanidin B2 in db/db Mice Reveal a Critical Role of Milk Fat Globule Epidermal Growth Factor-8 in Diabetic Arterial Damage

et al. 2012

PLoS ONE

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BackgroundAtherosclerosis is one of the major complications of type 2 diabetic patients (T2DM), leading to morbidity and mortality. Grape seed procyanidin B2 (GSPB2) has demonstrated protective effect against atherosclerosis, which is believed to be, at least in part, a result of its antioxidative effects. The aim of this study is to identify the target protein of GSPB2 responsible for the protective effect against atherosclerosis in patients with DM.Methods and ResultsGSPB2 (30 mg/kg body weight/day) were administrated to db/db mice for 10 weeks. Proteomics of the aorta extracts by iTRAQ analysis was obtained from db/db mice. The results showed that expression of 557 proteins were either up- or down-regulated in the aorta of diabetic mice. Among those proteins, 139 proteins were normalized by GSPB2 to the levels comparable to those in control mice. Among the proteins regulated by GSPB2, the milk fat globule epidermal growth factor-8 (MFG-E8) was found to be increased in serum level in T2DM patients; the serum level of MFG-E8 was positively correlated with carotid-femoral pulse wave velocity (CF-PWV). Inhibition of MFG-E8 by RNA interference significantly suppressed whereas exogenous recombinant MFG-E8 administration exacerbated atherogenesis the db/db mice. To gain more insights into the mechanism of action of MFG-E8, we investigated the effects of MFG-E8 on the signal pathway involving the extracellular signal-regulated kinase (ERK) and monocyte chemoattractant protein-1 (MCP-1). Treatment with recombinant MFG-E8 led to increased whereas inhibition of MFG-E8 to decreased expression of MCP-1 and phosphorylation of ERK1/2.ConclusionOur data suggests that MFG-E8 plays an important role in atherogenesis in diabetes through both ERK and MCP-1 signaling pathways. GSPB2, a well-studied antioxidant, significantly inhibited the arterial wall changes favoring atherogenesis in db/db mice by down-regulating MFG-E8 expression in aorta and its serum level. Measuring MFG-E8 serum level could be a useful clinical surrogate prognosticating atherogenesis in DM patients.

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“…CRP1 has been reported in many different cellular functions: acting as a transcriptional cofactor (Chang et al, 2003), suppressing cell proliferation, protecting cells from stress-induced death (Latonen et al, 2008), regulating cell movement during zebrafish development (Miyasaka et al, 2007), and promoting neointima formation (Lilly et al, 2010). It has also been demonstrated that CRP1 regulates actin filament bundling via direct interaction with actin (Tran et al, 2005;Jang and Greenwood, 2009).…”

Section: Introductionmentioning

confidence: 99%

CRP1, a Protein Localized in Filopodia of Growth Cones, Is Involved in Dendritic Growth

Ma¹,

Greenwood²,

Schachner³

2011

J. Neurosci.

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The cysteine-rich protein (CRP) family is a subgroup of LIM domain proteins. CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells. Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons. Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons. Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity. Expression of CRP1 with a constitutively active form of Cdc42, a GTPase involved in filopodia formation, increases filopodia formation in COS-7 cells, suggesting cooperation between the two proteins. Moreover, we demonstrate that neuronal activity upregulates CRP1 expression in hippocampal neurons via Ca 2ϩ influx after depolarization. Ca 2ϩ /calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein mediate the Ca 2ϩ -induced upregulation of CRP1 expression. Furthermore, CRP1 is required for the dendritic growth induced by Ca 2ϩ influx or CaMKIV. Together, these data are the first to demonstrate a role for CRP1 in dendritic growth.

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Loss of the Serum Response Factor Cofactor, Cysteine-Rich Protein 1, Attenuates Neointima Formation in the Mouse

Cited by 27 publications

References 37 publications

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Loss of LMOD1 impairs smooth muscle cytocontractility and causes megacystis microcolon intestinal hypoperistalsis syndrome in humans and mice

Proteomic Analysis of Aorta and Protective Effects of Grape Seed Procyanidin B2 in db/db Mice Reveal a Critical Role of Milk Fat Globule Epidermal Growth Factor-8 in Diabetic Arterial Damage

CRP1, a Protein Localized in Filopodia of Growth Cones, Is Involved in Dendritic Growth

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