LTBP1 promotes fibrillin incorporation into the extracellular matrix

Przyklenk, Matthias; Georgieva, Veronika S.; Metzen, Fabian; Mostert, Sebastian; Kobbe, Birgit; Callewaert, Bert; Sengle, Gerhard; Brachvogel, Bent; Mecham, Robert P.; Paulsson, Mats; Wagener, Raimund; Koch, Manuel; Schiavinato, Alvise

doi:10.1016/j.matbio.2022.04.004

Cited by 10 publications

(8 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This gene is involved in several important processes, including extracellular matrix organization, elastic fiber formation, and signaling by TGF-β family members. 117 There were no significant differential expressions in any of the genes between FFIK and FIIK. This confirmed the results obtained from the metabolomics analysis and might also be attributed to the ability of the HDF to adapt to a certain extent to changes in their microenvironment via modulating their cellular stiffness.…”

Section: Discussionmentioning

confidence: 84%

See 1 more Smart Citation

The Impact of Mechanical Cues on the Metabolomic and Transcriptomic Profiles of Human Dermal Fibroblasts Cultured in Ultrashort Self-Assembling Peptide 3D Scaffolds

Abdelrahman

Susapto

et al. 2023

ACS Nano

View full text Add to dashboard Cite

Cells' interactions with their microenvironment influence their morphological features and regulate crucial cellular functions including proliferation, differentiation, metabolism, and gene expression. Most biological data available are based on in vitro two-dimensional (2D) cellular models, which fail to recapitulate the three-dimensional (3D) in vivo systems. This can be attributed to the lack of cell−matrix interaction and the limitless access to nutrients and oxygen, in contrast to in vivo systems. Despite the emergence of a plethora of 3D matrices to address this challenge, there are few reports offering a proper characterization of these matrices or studying how the cell−matrix interaction influences cellular metabolism in correlation with gene expression. In this study, two tetrameric ultrashort self-assembling peptide sequences, FFIK and FIIK, were used to create in vitro 3D models using well-described human dermal fibroblast cells. The peptide sequences are derived from naturally occurring amino acids that are capable of self-assembling into stable hydrogels without UV or chemical cross-linking. Our results showed that 2D cultured fibroblasts exhibited distinct metabolic and transcriptomic profiles compared to 3D cultured cells. The observed changes in the metabolomic and transcriptomic profiles were closely interconnected and influenced several important metabolic pathways including the TCA cycle, glycolysis, MAPK signaling cascades, and hemostasis. Data provided here may lead to clearer insights into the influence of the surrounding microenvironment on human dermal fibroblast metabolic patterns and molecular mechanisms, underscoring the importance of utilizing efficient 3D in vitro models to study such complex mechanisms.

show abstract

Section: Discussionmentioning

confidence: 84%

“…This gene’s product transports latent transforming growth factor beta complexes to the extracellular matrix, where the latent cytokine is activated by a variety of processes. This gene is involved in several important processes, including extracellular matrix organization, elastic fiber formation, and signaling by TGF-β family members …”

Section: Discussionmentioning

confidence: 99%

The Impact of Mechanical Cues on the Metabolomic and Transcriptomic Profiles of Human Dermal Fibroblasts Cultured in Ultrashort Self-Assembling Peptide 3D Scaffolds

Abdelrahman

Susapto

et al. 2023

ACS Nano

View full text Add to dashboard Cite

show abstract

“…The expression level of Lox is reported to be acutely enhanced by BMP-2 via Smad4 and Runx2 [48]. As the activation molecules to the deposition of ECM components, LOX and LTBP1 (a protein assisting in the triggering of TGF-beta) are also reported to act as stimulators of the epithelial differentiation in skin and oral mucosa [26,[28][29][30]. In psoriatic skin, the epidermal keratinocytes exhibit a tendency towards hyperproliferation with elevated expression of SERPINE1 and ID1.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa

Mu,

Ono,

Nguyen

et al. 2024

Cells

View full text Add to dashboard Cite

The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial–mesenchymal cell co-culture models in the air–liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, IGF2, ID1, LTBP1, LOX, SERPINE1, IL24, and MMP1 as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism.

show abstract

“…Because Ltbp2 is broadly expressed both during embryonic development and in postnatal tissues, we examined multiple adult tissues for potential phenotypes. We focused on skin, bone, lung, and tissues where mutations in other LTBPs and functionally similar ECM proteins have exhibited phenotypes 23,36–58 . We were particularly interested in examining the role of LTBP2 in the cardiovascular system and bone since studies have shown correlations between single nucleotide polymorphisms in LTBP2 and human disease in both of these tissues 23,59 …”

Section: Introductionmentioning

confidence: 99%

Multi‐organ phenotypes in mice lacking latent TGFβ binding protein 2 (LTBP2)

Bodmer,

Knutsen,

Roth

et al. 2023

Developmental Dynamics

Self Cite

View full text Add to dashboard Cite

BackgroundLatent TGFβ binding protein‐2 (LTBP2) is a fibrillin 1 binding component of the microfibril. LTBP2 is the only LTBP protein that does not bind any isoforms of TGFβ, although it may interfere with the function of other LTBPs or interact with other signaling pathways.ResultsHere, we investigate mice lacking Ltbp2 (Ltbp2−/−) and identify multiple phenotypes that impact bodyweight and fat mass, and affect bone and skin development. The alterations in skin and bone development are particularly noteworthy since the strength of these tissues is differentially affected by loss of Ltbp2. Interestingly, some tissues that express high levels of Ltbp2, such as the aorta and lung, do not have a developmental or homeostatic phenotype.ConclusionsAnalysis of these mice show that LTBP2 has complex effects on development through direct effects on the extracellular matrix (ECM) or on signaling pathways that are known to regulate the ECM.

show abstract

LTBP1 promotes fibrillin incorporation into the extracellular matrix

Cited by 10 publications

References 63 publications

The Impact of Mechanical Cues on the Metabolomic and Transcriptomic Profiles of Human Dermal Fibroblasts Cultured in Ultrashort Self-Assembling Peptide 3D Scaffolds

The Impact of Mechanical Cues on the Metabolomic and Transcriptomic Profiles of Human Dermal Fibroblasts Cultured in Ultrashort Self-Assembling Peptide 3D Scaffolds

Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa

Multi‐organ phenotypes in mice lacking latent TGFβ binding protein 2 (LTBP2)

Contact Info

Product

Resources

About