Follistatin-like 1 and its paralogs in heart development and cardiovascular disease

Horák, Martin; Fairweather, DeLisa; Kokkonen, Piia; Bednář, David; Vašků, Julie Bienertová

doi:10.1007/s10741-022-10262-6

Cited by 14 publications

(5 citation statements)

References 134 publications

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“…Studies have observed that a catalytically inactive ADAMTS17 interferes with fibrillin-1 secretion, resulting in elastic fiber abnormalities and intracellular collagen accumulation in fibroblasts from patients with Weill-Marchesani syndrome (Karoulias et al, 2020). Another noteworthy protein involved in cell-matrix interactions is FSTL1, this is a secreted glycoprotein that participates in the regulation of the TGF-β, BMP and Wnt pathways (Hambrock et al, 2004; Horak et al, 2022). In axolotls, the identification of two domains, a Kasal and an EF-hand domain, aligns with the architecture described in other organisms (Li et al, 2019; Sylva et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Key Proteins for Regeneration inA. mexicanum: Transcriptomic Insights from Aged and Juvenile Limbs

del Moral-Morales,

Sámano,

Ocampo-Cervantes

et al. 2023

Preprint

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The axolotl is an animal with remarkable regenerative abilities, making it an ideal model for studying potential regenerative therapies in mammals, including humans. However, the molecular mechanisms involved in regeneration remain unclear. We conducted a transcriptomic analysis of juvenile axolotls’ limbs and their blastema and compared the results with aged axolotls that failed to regenerate after amputation. We identified a set of genes involved in cell differentiation, transcriptional regulation, cartilage development, bone morphogenesis, and extracellular matrix remodeling. Four highly expressed genes (FSTL1, ADAMTS17, GPX7, andCTHRC1) were identified in regenerating tissue, but underexpressed in aged axolotls. Structural and homology analysis showed that these genes are conserved and have important roles in development, bone morphogenesis, and cartilage formation. Our findings propose a novel set of axolotl genes involved in tissue regeneration that could be a starting point for further studies in other vertebrates.Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Key Proteins for Regeneration inA. mexicanum: Transcriptomic Insights from Aged and Juvenile Limbs

del Moral-Morales,

Sámano,

Ocampo-Cervantes

et al. 2023

Preprint

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“…Although previous studies have demonstrated a positive association between FSTL-1 levels and in ammation, a strong association between the two factors was not observed in our study 1 . Previous studies have identi ed high FSTL-1 levels in various in ammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, or systemic sclerosis 1,33 . High FSTL-1 levels in in ammatory diseases are associated with poor clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

Clinical Implications of Circulating Follistatin-like Protein-1 in Hemodialysis Patients

Kim

Kang

Kim

et al. 2023

Preprint

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Follistatin-like protein-1 (FSTL-1) is secreted glycoprotein, which regulates cardiovascular, immune and skeletal system. However, the clinical significance of circulating FSTL-1 levels remains unclear in hemodialysis patients. A total 376 hemodialysis patients were prospectively enrolled from June 2016 to March 2020. Plasma FSTL-1 level, inflammatory biomarkers, physical performance, and echocardiographic findings at baseline were examined. The primary endpoint was defined as a composite of incident CV events and death. Plasma FSTL-1 levels were positively correlated with TNF-α and MCP-1. Handgrip strength showed weak positive correlation in male patients only. In multivariate linear regression analysis, FSTL-1 level was negatively associated with left ventricular ejection fraction (β = −0.36; p = 0.011). Both cumulative event rate of the composite of CV event and death, and cumulative event rate of CV events were significantly greater in FSTL-1 tertile 3. In Cox regression analysis, FSTL-1 tertile 3 was associated with a 1.80-fold risk for the composite of CV events and death(95% confidence interval (CI), 1.06–3.08), and a 2.29-fold risk for CV events (95% CI, 1.15–4.54) after adjustment for multiple variables. In conclusion, high circulating FSTL-1 levels independently predict the composite of CV events and death, and FSTL-1 level was independently associated with left ventricular systolic dysfunction.

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“…The primary transcript encodes microRNA (miR)-198. The product is a secreted glycoprotein, FSTL1 with activities in angiogenesis, cell proliferation, differentiation, embryogenesis, metastasis, and wound healing; specifically reducing inflammation and fibrosis in cardiovascular disease [43,[115][116][117][118]. Notably, Fstl1 affects survival of M. tuberculosis-infected macrophages [34,35,119].…”

Section: Discussionmentioning

confidence: 99%

Systems genetics uncover new loci containing functional gene candidates inMycobacterium tuberculosis-infected Diversity Outbred mice

Gatti,

Tyler,

Mahoney

et al. 2023

Preprint

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Mycobacterium tuberculosis,the bacillus that causes tuberculosis (TB), infects 2 billion people across the globe, and results in 8-9 million new TB cases and 1-1.5 million deaths each year. Most patients have no known genetic basis that predisposes them to disease. We investigated the complex genetic basis of pulmonary TB by modelling human genetic diversity with the Diversity Outbred mouse population. When infected withM. tuberculosis, one-third develop early onset, rapidly progressive, necrotizing granulomas and succumb within 60 days. The remaining develop non-necrotizing granulomas and survive longer than 60 days. Genetic mapping using clinical indicators of disease, granuloma histopathological features, and immune response traits identified five new loci on mouse chromosomes 1, 2, 4, 16 and three previously identified loci on chromosomes 3 and 17. Quantitative trait loci (QTLs) on chromosomes 1, 16, and 17, associated with multiple correlated traits and had similar patterns of allele effects, suggesting these QTLs contain important genetic regulators of responses toM. tuberculosis. To narrow the list of candidate genes in QTLs, we used a machine learning strategy that integrated gene expression signatures from lungs ofM. tuberculosis-infected Diversity Outbred mice with gene interaction networks, generating functional scores. The scores were then used to rank candidates for each mapped trait in each locus, resulting in 11 candidates:Ncf2, Fam20b, S100a8, S100a9, Itgb5, Fstl1, Zbtb20, Ddr1, Ier3, Vegfa,andZfp318. Importantly, all 11 candidates have roles in infection, inflammation, cell migration, extracellular matrix remodeling, or intracellular signaling. Further, all candidates contain single nucleotide polymorphisms (SNPs), and some but not all SNPs were predicted to have deleterious consequences on protein functions. Multiple methods were used for validation including (i) a statistical method that showed Diversity Outbred mice carrying PWH/PhJ alleles on chromosome 17 QTL have shorter survival; (ii) quantification of S100A8 protein levels, confirming predicted allele effects; and (iii) infection of C57BL/6 mice deficient for theS100a8gene. Overall, this work demonstrates that systems genetics using Diversity Outbred mice can identify new (and known) QTLs and new functionally relevant gene candidates that may be major regulators of granuloma necrosis and acute inflammation in pulmonary TB.

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Follistatin-like 1 and its paralogs in heart development and cardiovascular disease

Cited by 14 publications

References 134 publications

Key Proteins for Regeneration inA. mexicanum: Transcriptomic Insights from Aged and Juvenile Limbs

Key Proteins for Regeneration inA. mexicanum: Transcriptomic Insights from Aged and Juvenile Limbs

Clinical Implications of Circulating Follistatin-like Protein-1 in Hemodialysis Patients

Systems genetics uncover new loci containing functional gene candidates inMycobacterium tuberculosis-infected Diversity Outbred mice

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