Fibulin-6 regulates pro-fibrotic TGF-β responses in neonatal mouse ventricular cardiac fibroblasts

Chowdhury, Arpita; Hasselbach, Lisa; Echtermeyer, Frank; Jyotsana, Nidhi; Theilmeier, Gregor; Herzog, Christine

doi:10.1038/srep42725

Cited by 19 publications

(23 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…That HMCN1 proteins assemble into tracks suggests a role for HMCN1 in structural support. Data from a mouse model of myocardial infarction and from cultured cardiac fibroblasts suggest that HMCN1 functions in myocardial remodeling by regulating profibrotic TGB‐β responses . It is possible that HMCN1 also plays important roles in remodeling of the tissues examined in our study during development and in response to injury.…”

Section: Discussionmentioning

confidence: 81%

Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues

Lin

Pope

Sasaki

et al. 2020

Developmental Dynamics

View full text Add to dashboard Cite

Background: Hemicentins (HMCNs) are a family of extracellular matrix proteins first identified in Caenorhabditis elegans, with two orthologs (HMCN1 and 2) in vertebrates. In worms, HMCN is deposited at specific sites where it forms long, fine tracks that link two tissues by connecting adjacent basement membranes (BMs). By generating CRISPR/Cas9-mediated Hmcn1 and Hmcn2 knockout mice, we tested the hypothesis that HMCNs perform similar functions in mammals.Results: Hmcn1 −/− mice were viable and fertile. Using new, knockout mousevalidated HMCN1 antibodies, HMCN1 was detected in wild-type mice as fine tracks along the BM of hair and whisker follicles, in the sclera of the eyes, and in the lumen of some lymphoid conduits. It was also observed in the mesangial matrix of the kidney glomerulus. However, HMCN1 deficiency did not affect the functions of these tissues, including adherence of coat hairs and whiskers, the sieving function of lymphoid conduits, or the immune response to injected antigens. HMCN2 deficiency did not lead to any discernible phenotypes on its own or when combined with HMCN1 deficiency.Conclusion: That Hmcn1 −/− , Hmcn2 −/− , and Hmcn1/2 double knockout mice did not display any overt phenotypes implicates compensation by other members of the fibulin family. K E Y W O R D Sbasement membrane, hair follicle, lymphoid conduits, matrix protein, sclera, whisker follicle

show abstract

Section: Discussionmentioning

confidence: 81%

Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues

Lin

Pope

Sasaki

et al. 2020

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…Insulin and contraction are the two key stimuli that acutely regulate Glut4 recruitment to the plasma membrane of the heart, and cardiac fibroblast contractility is one of the characteristics of myocardial remodeling [ 44 ]. These two stimuli initiate distinct signaling mechanisms, but both lead to increased Glut 4 translocation and glucose uptake [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Glycosides from Stevia rebaudiana Bertoni Possess Insulin‐Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts

Prata

Zambonin

Rizzo

et al. 2017

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Stevia rebaudiana Bertoni is a shrub having a high content of sweet diterpenoid glycosides in its leaves, mainly stevioside and rebaudioside A, which are used as noncaloric, natural sweeteners. The aim of this study was to deepen the knowledge about the insulin-mimetic effect exerted by four different mixtures of steviol glycosides, rich in stevioside and rebaudioside A, in neonatal rat cardiac fibroblasts. The potential antioxidant activity of these steviol glycosides was also assessed, as oxidative stress is associated with diabetes. Likewise the insulin effect, steviol glycosides caused an increase in glucose uptake into rat fibroblasts by activating the PI3K/Akt pathway, thus inducing Glut4 translocation to the plasma membrane. The presence of S961, an insulin antagonist, completely abolished these effects, allowing to hypothesize that steviol glycosides could act as ligands of the same receptor engaged by insulin. Moreover, steviol glycosides counteracted oxidative stress by increasing reduced glutathione intracellular levels and upregulating expression and activity of the two antioxidant enzymes superoxide dismutase and catalase. The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance.

show abstract

“…Fibulin-6 is upregulated in the ischemic myocardium, especially in the infarct border zone, but, paradoxically, TGF-β treatment in isolated mouse cardiac fibroblasts inhibits fibulin-6 expression, indicating complex involvement of fibulin-6 in TGF-β signaling [ 147 ]. Further investigation by the same group demonstrated that fibulin-6 plays an important role in regulating TGF-β-mediated responses by enhancing TGF-β receptor dimerization and activation to further trigger downstream pathways [ 148 ]. The interaction between other newer fibulins, fibulin-7 and -8, and TGF-β has not been identified.…”

Section: Interaction Between Fibulins and Tgf-βmentioning

confidence: 99%

“…Fibulin-5 expression is enhanced by TGF-β [ 121 , 122 , 142 , 146 ], and fibulin-5 promotes TGF-β-induced EMT through activating MMP-2 and -9 in mammary epithelial cells [ 122 ], suggesting bidirectional interaction similar to fibulin-2. Fibulin-6 plays a role in negative feedback loop in regulating TGF-β-mediated profibrotic response in neonatal mouse ventricular cardiac fibroblasts [ 148 ], similar to fibulin-1. Each fibulin appears to have a unique biological profile in relation to TGF-β signaling in a context-dependent manner.…”

Section: Biological Significance Of Fibulins and Tgf-β Signalingmentioning

confidence: 99%

Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions

Tsuda

2018

IJMS

View full text Add to dashboard Cite

Transforming growth factor (TGF)-β is a multifunctional peptide growth factor that has a vital role in the regulation of cell growth, differentiation, inflammation, and repair in a variety of tissues, and its dysregulation mediates a number of pathological conditions including fibrotic disorders, chronic inflammation, cardiovascular diseases, and cancer progression. Regulation of TGF-β signaling is multifold, but one critical site of regulation is via interaction with certain extracellular matrix (ECM) microenvironments, as TGF-β is primarily secreted as a biologically inactive form sequestrated into ECM. Several ECM proteins are known to modulate TGF-β signaling via cell–matrix interactions, including thrombospondins, SPARC (Secreted Protein Acidic and Rich in Cystein), tenascins, osteopontin, periostin, and fibulins. Fibulin family members consist of eight ECM glycoproteins characterized by a tandem array of calcium-binding epidermal growth factor-like modules and a common C-terminal domain. Fibulins not only participate in structural integrity of basement membrane and elastic fibers, but also serve as mediators for cellular processes and tissue remodeling as they are highly upregulated during embryonic development and certain disease processes, especially at the sites of epithelial–mesenchymal transition (EMT). Emerging studies have indicated a close relationship between fibulins and TGF-β signaling, but each fibulin plays a different role in a context-dependent manner. In this review, regulatory interactions between fibulins and TGF-β signaling are discussed. Understanding biological roles of fibulins in TGF-β regulation may introduce new insights into the pathogenesis of some human diseases.

show abstract

Fibulin-6 regulates pro-fibrotic TGF-β responses in neonatal mouse ventricular cardiac fibroblasts

Cited by 19 publications

References 41 publications

Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues

Mammalian hemicentin 1 is assembled into tracks in the extracellular matrix of multiple tissues

Glycosides from Stevia rebaudiana Bertoni Possess Insulin‐Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts

Extracellular Interactions between Fibulins and Transforming Growth Factor (TGF)-β in Physiological and Pathological Conditions

Contact Info

Product

Resources

About