Elevated prolidase activity in keloids: correlation with type I collagen turnover

Hs, Duong; Qz, Zhang; Ad, Lê; Ap, Kelly; Kamdar, Ruby S.; Dv, Messadi

doi:10.1111/j.1365-2133.2006.07167.x

Cited by 22 publications

(16 citation statements)

References 43 publications

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“…In adipose tissue, adiponectin lowers inflammation and increases glucose uptake, fat storage and adipogenesis; in muscle induces an increased fatty acid oxidation; in heart decreases injury and apoptosis; in endothelium decreases oxidative stress and increases angiogenesis and function; in liver increases insulin sensitivity and lowers gluconeogenesis and lipogenesis; in macrophages increases insulin sensitivity and lowers inflammation. Thus it remains to be investigated, if SNPs with pleiotropic associations to the two phenotypes HDLC and adiponectin are flagging any anti-inflammatory and/or MetS protective effects from these genes ( LYPLAL1 , GRB14 , COBLL1 , STAB1 , NT5DC2 , FAM13A , SLC39A8 , ARL15 , VEGFA , HCAR2 [127], ZNF664 , CMIP [128], and PEPD [120, 129, 130]).…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic genes for metabolic syndrome and inflammation

Kraja¹,

Chasman²,

North³

et al. 2014

Molecular Genetics and Metabolism

123

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Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic associations across phenotypes and might explain a part of MetS correlated genetic architecture. These findings warrant further functional investigation.

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Section: Discussionmentioning

confidence: 99%

Pleiotropic genes for metabolic syndrome and inflammation

Kraja¹,

Chasman²,

North³

et al. 2014

Molecular Genetics and Metabolism

123

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“…Although it is unlikely that complete loss of PEPD function alters AAA risk, given that it results in the severe phenotype of prolidase deficiency, polymorphisms that alter PEPD activity could contribute to AAA formation, particularly if they resulted in increased enzymatic activity [46]. Increased PEPD activity has been associated with increased collagen production, both in in vitro experiments [21,47] and in keloid scars [48]. Excess collagen production is observed in AAA tissue [49], and has been suggested to contribute to weakening of the aneurysm wall [50].…”

Section: Discussionmentioning

confidence: 99%

Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19

et al. 2011

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BackgroundAbdominal aortic aneurysm (AAA) is a complex disorder with multiple genetic risk factors. Using affected relative pair linkage analysis, we previously identified an AAA susceptibility locus on chromosome 19q13. This locus has been designated as the AAA1 susceptibility locus in the Online Mendelian Inheritance in Man (OMIM) database.MethodsNine candidate genes were selected from the AAA1 locus based on their function, as well as mRNA expression levels in the aorta. A sample of 394 cases and 419 controls was genotyped for 41 SNPs located in or around the selected nine candidate genes using the Illumina GoldenGate platform. Single marker and haplotype analyses were performed. Three genes (CEBPG, PEPD and CD22) were selected for DNA sequencing based on the association study results, and exonic regions were analyzed. Immunohistochemical staining of aortic tissue sections from AAA and control individuals was carried out for the CD22 and PEPD proteins with specific antibodies.ResultsSeveral SNPs were nominally associated with AAA (p < 0.05). The SNPs with most significant p-values were located near the CCAAT enhancer binding protein (CEBPG), peptidase D (PEPD), and CD22. Haplotype analysis found a nominally associated 5-SNP haplotype in the CEBPG/PEPD locus, as well as a nominally associated 2-SNP haplotype in the CD22 locus. DNA sequencing of the coding regions revealed no variation in CEBPG. Seven sequence variants were identified in PEPD, including three not present in the NCBI SNP (dbSNP) database. Sequencing of all 14 exons of CD22 identified 20 sequence variants, five of which were in the coding region and six were in the 3'-untranslated region. Five variants were not present in dbSNP. Immunohistochemical staining for CD22 revealed protein expression in lymphocytes present in the aneurysmal aortic wall only and no detectable expression in control aorta. PEPD protein was expressed in fibroblasts and myofibroblasts in the media-adventitia border in both aneurysmal and non-aneurysmal tissue samples.ConclusionsAssociation testing of the functional positional candidate genes on the AAA1 locus on chromosome 19q13 demonstrated nominal association in three genes. PEPD and CD22 were considered the most promising candidate genes for altering AAA risk, based on gene function, association evidence, gene expression, and protein expression.

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“…Previously, it has been shown that prolidase activity in normal fibroblasts is regulated by the interaction of extracellular matrix proteins, mainly type I collagen with b 1 -integrin receptor (Palka and Phang, 1997) and b 1 -integrin-dependent signaling (Surazynski et al, 2005). Previous clinical studies have shown increased serum prolidase activity, which indicates increased collagen turnover, in chronic liver disease (Myara et al, 1984), osteoporosis (Erbagci et al, 2002), osteoarthritis (Altindag et al, 2007), Helicobacter pylori gastritis (Aslan et al, 2007), breast cancer (CechowskaPasko et al, 2006), wound healing (Senboshi et al, 1996), and keloid formation (Duong et al, 2006). Serum prolidase activity was reported to be increased in patients with hypertension (Demirbag et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

The Association of Serum Prolidase Activity and Erectile Dysfunction

Savaş

Yeni

Çelik

et al. 2010

Journal of Andrology

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Prolidase is a cytosolic exopeptidase that cleaves iminodipeptides with carboxy-terminal proline or hydroxyproline and plays a major role in collagen turnover. Collagen is the essential content in atherosclerotic plaque, playing a key role in the stability/ instability and progression of endothelial dysfunction in the pathogenesis of erectile dysfunction (ED). Consequently, in this study we sought to determine serum prolidase activity and markers of oxidative stress, such as lipid hydroperoxide and total free sulfhydryl, in vasculogenic ED. We evaluated 92 patients with vasculogenic ED and 50 control subjects by clinical and laboratory investigations. We measured serum prolidase activity and serum total free sulfhydryl levels spectrophotometrically. Serum lipid hydroperoxide levels were determined with ferrous ion oxidationxylenol orange method. We assessed the association of serum prolidase activity with the presence and severity of vasculogenic ED and clinical characteristics, as well as laboratory parameters. We also assessed the association of serum prolidase activity with the variables according to the vascular status of patients with vasculogenic ED. The comparison included 92 vasculogenic ED patients grouped into 3 categories according to the vascular status of patients with ED-arterial insufficiency (n 5 26), veno-occlusive dysfunction (n 5 37), and mixed-type impotence (n 5 29)-and 50 controls. Receiver-operator characteristics (ROCs) were analyzed to find a cutoff value with the best sensitivity and lowest falsepositive rate. Serum prolidase activity (53.5 6 5.5 U/L vs 45.7 6 4.9 U/L, respectively; P , .001) and serum lipid hydroperoxide levels were significantly increased in patients with vasculogenic ED compared with controls, whereas serum total free sulfhydryl levels were significantly decreased in patients with vasculogenic ED compared with controls (P , .001). The lowest and highest mean serum prolidase activities were detected in control participants and in patients with arterial insufficiency, respectively (analysis of variance P , .001). The overall findings of this study support the predictive accuracy of the serum prolidase activity in our cohort, with a statistically significant ROC value of 0.78. Findings of this study have shown that serum prolidase activity is significantly associated with the presence and severity of vasculogenic ED, and elevated serum prolidase activity might be an independent predictor of ED.

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Elevated prolidase activity in keloids: correlation with type I collagen turnover

Abstract: The combination of elevated prolidase activity and associated higher collagen synthesis to degradation ratio in keloids suggests a possible metabolic process for the excessive accumulation of type I collagen in keloids.

Cited by 22 publications

References 43 publications

Pleiotropic genes for metabolic syndrome and inflammation

Pleiotropic genes for metabolic syndrome and inflammation

Analysis of positional candidate genes in the AAA1 susceptibility locus for abdominal aortic aneurysms on chromosome 19

The Association of Serum Prolidase Activity and Erectile Dysfunction

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