Aberrant interaction between mutated ADAMTSL2 and LTBP4 is associated with adolescent idiopathic scoliosis

Liu, Bowen; Zhao, Sen; Lian, Ling; Du, Huakang; Zhao, Hengqiang; Wang, Shengru; Niu, Yuchen; Li, Xiaoxin; Qiu, Guixing; Wu, Zhihong; Zhang, Terry Jianguo; Wu, Nan

doi:10.1016/j.gene.2021.146126

Cited by 7 publications

(9 citation statements)

References 42 publications

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“…The ability to bind fibrillin microfibrils was demonstrated for all ADAMTSL family members, except ADAMTSL1. Most ADAMTSLs bind fibrillin-1, and several also bind fibrillin-2, as well as microfibril-associated molecules e.g., LTBPs, TGFβ, ADAMTS10, heparin and LOX [ 17 , 19 – 23 ] (Fig. 2 ).…”

Section: Cardiovascular Disease Is a Major Cause Of Morbidity And Mor...mentioning

confidence: 99%

“…No cardiovascular phenotype is described. ADAMTSL2 Geleophysic dysplasia (MIM 231050), Al Gazali skeletal dysplasia (MIM 601356) 3.55 54.51 3.13 13.66 Fibrillin-1/2 [ 11 ], LTBP1 [ 10 ], LTBP4 [ 23 ], LOX [ 20 ] Mouse Adamtsl2 -/- [ 11 ] Knockout mice die after birth from bronchial occlusion, characterized by peribronchial fibrillin-2 accumulation, and increased TGFβ signaling [ 11 ]. Ventricular septal defect was observed.…”

Section: Cardiovascular Disease Is a Major Cause Of Morbidity And Mor...mentioning

confidence: 99%

“…The largest body of evidence supports a role for ADAMTSL2 in suppression of TGFβ activity, as ADAMTSL2 localizes to microfibrils and binds directly to fibrillin-1 and fibrillin-2 in cultured fibroblasts [ 11 ]. ADAMTSL2 also binds LTBP1 [ 19 , 38 ] and LTBP4 [ 23 ], suggesting it is part of a TGFβ sequestering complex (Fig. 2 ).…”

Section: Cardiovascular Disease Is a Major Cause Of Morbidity And Mor...mentioning

confidence: 99%

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Emerging roles for the ADAMTS-like family of matricellular proteins in cardiovascular disease through regulation of the extracellular microenvironment

Rypdal,

Apte,

Lunde

2024

Mol Biol Rep

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Dysregulation of the extracellular matrix (ECM) occurs widely across cardiovascular pathologies. Recent work has revealed important roles for the «a disintegrin-like and metalloprotease domain with thrombospondin-type 1 motifs like” (ADAMTSL) family of secreted glycoproteins in cardiovascular tissues during development and disease. Key insights in this regard have come from naturally occurring gene mutations in humans and animals that result in severe diseases with cardiovascular manifestations or aortopathies. Expression of ADAMTSL genes is greatly increased in the myocardium during heart failure. Genetically modified mice recapitulate phenotypes of patients with ADAMTSL mutations and demonstrate important functions in the ECM. The novel functions thus disclosed are intriguing because, while these proteins are neither structural, nor proteases like the related ADAMTS proteases, they appear to act as regulatory, i.e., matricellular proteins. Evidence from genetic variants, genetically engineered mouse mutants, and in vitro investigations have revealed regulatory functions of ADAMTSLs related to fibrillin microfibrils and growth factor signaling. Interestingly, the ability to regulate transforming growth factor (TGF)β signaling may be a shared characteristic of some ADAMTSLs. TGFβ signaling is important in cardiovascular development, health and disease and a central driver of ECM remodeling and cardiac fibrosis. New strategies to target dysregulated TGFβ signaling are warranted in aortopathies and cardiac fibrosis. With their emerging roles in cardiovascular tissues, the ADAMTSL proteins may provide causative genes, diagnostic biomarkers and novel treatment targets in cardiovascular disease. Here, we discuss the relevance of ADAMTSLs to cardiovascular medicine.

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Section: Cardiovascular Disease Is a Major Cause Of Morbidity And Mor...mentioning

confidence: 99%

Section: Cardiovascular Disease Is a Major Cause Of Morbidity And Mor...mentioning

confidence: 99%

Section: Cardiovascular Disease Is a Major Cause Of Morbidity And Mor...mentioning

confidence: 99%

See 1 more Smart Citation

Emerging roles for the ADAMTS-like family of matricellular proteins in cardiovascular disease through regulation of the extracellular microenvironment

Rypdal,

Apte,

Lunde

2024

Mol Biol Rep

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“…При этом в отдельную группу можно вынести гены, коррелирующие не с наличием ИС, а с его тяжестью. Корреляция с наличием ИС хотя бы в одном исследовании выявлена в отношении генов MAPK7 [14] и аллельный маркер DS1034 в хромосоме 19p13.3 [15], LBX1 [16], MATN1 (матрилин 1) [17], ESR2 (рецептор эстрогенов бета) [18], BMP4, IL-6 (интерлейкин-6), leptin, MMP3, MTNR1B (рецептор мелатонина 1b) [19], CALM1 (кальмодулин 1) [20], VDR (рецептор витамина Д) [21], TPH1 (триптофангидроксилаза 2) [22], FBN1 (фибриллин-1) и FBN2 (фибриллин-2) [23], COL11A1, COL11A2 и TGFBR2 [24], GPR126 (G-белок, связанный с рецептором 126) [25], PAX1 (парный бокс 1) [26], TGFB1 (трансформирующий фактор роста бета 1) [27], C17orf67 и DOT1L [28], IL-17RC (интер-лейкин 17 рецептор C) [29], POC5 (центриолярный белок) [30], NUCKS1 (ядерная казеинкиназа и циклин-зависимая киназа субстрат 1) [31], гомеобокс гены HOXB8, HOXB7, HOXA13, HOXA10), ZIC2, FAM101A (регулятор белка филамина А), COMP (олигомерный матриксный белок хряща) и PITX1 (парный гомеодоменный фактор транскрипции) [32,33].…”

Section: генетическая теорияunclassified

Idiopathic scoliosis as a multifactorial disease: systematic review of current literature

Sergeenko

Щурова

2022

Hir. pozvonoč.

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Objective. To analyze the current literature dedicated to the etiopathogenesis and development of idiopathic scoliosis.Material and Methods. The analysis includes studies on the etiological factors of idiopathic scoliosis. The search was carried out on eLibrary, PubMed and Google Scholar databases. The review includes research and experimental studies, as well as systematic reviews and meta-analyses. The exclusion criterion is a theoretical work without practical research/experiment to confirm the theory. The depth of analysis is 30 years.Results. Out of 456 papers on the research topic, 153 were selected as meeting the inclusion/exclusion criteria. The main theories of the occurrence of idiopathic scoliosis are identified: genetic, neurogenic, theory of bone and muscle tissue defects, biomechanical, hormonal, evolutionary, and the theory of environmental and lifestyle influences.Conclusions. The term “idiopathic scoliosis” combines a number of diseases with different etiopathogenetic mechanisms of development. Idiopathic scoliosis has a polygenic inheritance. Different genes are responsible for its occurrence in different populations, and the progression mechanisms are triggered by various epigenetic factors. Bone and muscle tissue defects, pathology of the central nervous system, biomechanical disturbances, hormonal and biochemical abnormalities may play a dominant role in some cases of idiopathic scoliosis.

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“…At present, researchers are focusing heavily on gene polymorphism, which is considered to play an important role in the pathogenesis of AIS. The single nucleotide polymorphism (SNP) of the estrogen receptor β (ESR2) gene ( 10 , 14 , 15 ), vitamin D receptor ( 16-18 ), insulin-like growth factor-1 (IGF1) ( 19 , 20 ), melatonin receptor ( 21 ), ADAMTS-like protein 2 (ADAMTSL2), latent transforming growth factor β-binding protein 4 (LTBP4), Ras homolog gene family, member A (RHOA) ( 12 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Association of IL‑6 and MMP‑3 gene polymorphisms with adolescent idiopathic scoliosis: A systematic review and meta‑analysis

Wang,

Qin,

Yang

et al. 2024

Exp Ther Med

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The pathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear. It has been found that interleukin-6 (IL-6) rs1800795 locus and matrix metalloproteinase-3 (MMP-3) rs3025058 locus gene polymorphisms may be associated with AIS susceptibility, which has been controversial and needs to be further confirmed by updated meta-analysis. The aim of the present study was to investigate the association of MMP-3 rs3025058 and IL-6 rs1800795 single nucleotide polymorphisms (SNPs) with susceptibility to AIS. All relevant articles that met the criteria were retrieved and included, and the publication dates were limited from January 2005 to December 2023. The allele frequencies and different genotype frequencies of IL-6 rs1800795 and MMP-3 rs3025058 loci in each study were extracted and statistically analyzed by ReviewManager 5.4 software, and the odds ratio (OR) and 95% confidence interval (95% CI) of different genetic models were calculated. The results of the meta-analysis showed that there was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS. The allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility (5A vs. 6A, OR=1.18; 95% CI, 1.04-1.33; 5A5A vs. 6A6A, OR=1.65; 95% CI, 1.23-2.21; and 5A5A vs. 5A6A + 6A6A, OR=1.54; 95% CI, 1.19-1.99). Results of subgroup analysis revealed that the allele 5A and genotype 5A5A of MMP-3 rs3025058 SNP were associated with AIS susceptibility in the Caucasian population, and the susceptibility of AIS was associated with the genotype 5A5A of MMP-3 rs3025058 SNP in an Asian population. There was no significant association between the gene polymorphism of IL-6 rs1800795 locus and the pathogenesis of AIS, while the allele 5A of MMP-3 rs3025058 locus was associated with the susceptibility to AIS, especially in the Caucasian population.

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Aberrant interaction between mutated ADAMTSL2 and LTBP4 is associated with adolescent idiopathic scoliosis

Cited by 7 publications

References 42 publications

Emerging roles for the ADAMTS-like family of matricellular proteins in cardiovascular disease through regulation of the extracellular microenvironment

Emerging roles for the ADAMTS-like family of matricellular proteins in cardiovascular disease through regulation of the extracellular microenvironment

Idiopathic scoliosis as a multifactorial disease: systematic review of current literature

Association of IL‑6 and MMP‑3 gene polymorphisms with adolescent idiopathic scoliosis: A systematic review and meta‑analysis

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