Laminin-521 promotes quiescence in isolated stellate cells from rat liver

Rohn, Friederike; Kordes, Claus; Castoldi, Mirco; Götze, Silke; Poschmann, Gereon; Herebian, Diran; Benk, Amelie S.; Geiger, Fania; Zhang, Tingyu; Spatz, Joachim P.; Häussinger, Dieter

doi:10.1016/j.biomaterials.2018.07.008

Cited by 16 publications

(15 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their ultimate behavior is most likely controlled by environmental factors and, thus, by their stem cell niche. The importance of the presence of specific ECM proteins in the microenvironment for the maintenance of HSC characteristics was demonstrated recently, since it has been shown that LN‐521 promotes the quiescent state of isolated HSC and that the LAMA5 chain is present in the space of Disse (Rohn et al, 2018). Although the LAMA5 amount remained unchanged during aging as observed in the present study, LAMB2 and LAMC1 showed a marked reduction in the liver tissue of old rats.…”

Section: Discussionmentioning

confidence: 99%

“…In a different approach, nanostructured surfaces were generated by binding laminin to gold dots with an average spacing of 151 ± 35 nm. These gold dots were bio‐functionalized with LN‐211 or LN‐521 (BioLamina) as described (Rohn et al, 2018). HSC from mid‐aged rats were seeded directly after isolation on nanostructured surfaces and cultured under serum‐free conditions.…”

Section: Methodsmentioning

confidence: 99%

“…HSC are liver‐resident mesenchymal stem cells which reside in the space of Disse between sinusoidal endothelial cells (SEC) and hepatocytes. This unique space contains a basement membrane‐like structure composed of laminins and collagen IV (COL4) and serves as a stem cell niche for stellate cells (Kordes & Häussinger, 2013; Kordes, Sawitza, Götze, & Häussinger, 2013; Rohn et al, 2018; Sawitza, Kordes, Reister, & Häussinger, 2009). In chronic liver diseases, HSC become activated and develop into myofibroblast‐like cells which contribute to fibrogenesis (Kisseleva et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…HSC‐derived myofibroblasts show an increased expression of α‐smooth muscle actin (α‐SMA) and collagen I (COL1) and a downregulation of quiescence markers such as glial fibrillary acidic protein (GFAP; Gard, White, & Dutton, 1985). The activation of HSC is reversible as demonstrated in fibrotic liver and culture of HSC‐derived myofibroblast‐like cells on laminin‐521 (LN‐521; Kisseleva et al, 2012; Rohn et al, 2018). HSC fulfill important functions as mesenchymal stem cells during liver homeostasis and regeneration (Kordes, Sawitza, Götze, Schumacher, & Häussinger, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Characteristics of quiescent HSC are maintained in their perivascular niche, the space of Disse. Here, ECM components such as LN‐521 are involved in HSC maintenance (Rohn et al, 2018). The heterotrimeric laminin chains LN‐521 and LN‐511 are important to maintain stem cell characteristics (Domogatskaya, Rodin, Boutaud, & Tryggvason, 2008; Rodin, Antonsson, Hovatta, & Tryggvason, 2014) and are synthesized by pericytes (Jeon et al, 1996) and endothelial cells as reported for the kidney, cornea, skin, and lymph nodes (Miner, 2012; Okumura et al, 2015; Sorokin et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Impaired integrin α₅/β₁‐mediated hepatocyte growth factor release by stellate cells of the aged liver

et al. 2020

Self Cite

View full text Add to dashboard Cite

horseradish peroxidase; HSC, hepatic stellate cells; IL6, interleukin-6; IMDM, Iscove's Modified Dulbecco's Medium; ITGA5, integrin α 5 ; ITGB1, integrin β 1 ; ITS, insulin-selenitetransferrin; LAMA2, laminin α2; LAMA4, laminin α4; LAMA5, laminin α5; LAMB1, laminin β1; LAMB2, laminin β2; LAMC1, laminin γ1; LN-211, laminin-211; LN-521, laminin-521; LRAT, lecithin-retinol acyltransferase; MMP13, metalloproteinase 13; NGF, nerve growth factor; NID, nidogen; PBS, phosphate buffered saline; PCA, principal component analysis; PEG, polyethylene glycol; PPARγ, peroxisome proliferator-activated receptor γ; qPCR, quantitative polymerase chain reaction; SASP, senescence-associated secretory phenotype; SEC, sinusoidal endothelial cells; SEM, standard error of the mean; SPARCL1, secreted protein acidic and rich in cysteines-like 1; TGFb, transforming growth factor β; TLN, talin; TNFR, tumor necrosis factor receptor; VCL, vinculin; α-SMA, α-smooth muscle actin. AbstractHepatic blood flow and sinusoidal endothelial fenestration decrease during aging.Consequently, fluid mechanical forces are reduced in the space of Disse where hepatic stellate cells (HSC) have their niche. We provide evidence that integrin α 5 /β 1 is an important mechanosensor in HSC involved in shear stress-induced release of hepatocyte growth factor (HGF), an essential inductor of liver regeneration which is impaired during aging. The expression of the integrin subunits α 5 and β 1 decreases in liver and HSC from aged rats. CRISPR/Cas9-mediated integrin α 5 and β 1 knockouts in isolated HSC lead to lowered HGF release and impaired cellular adhesion. Fluid mechanical forces increase integrin α 5 and laminin gene expression whereas integrin β 1 remains unaffected. In the aged liver, laminin β2 and γ1 protein chains as components of laminin-521 are lowered. The integrin α 5 knockout in HSC reduces laminin expression via mechanosensory mechanisms. Culture of HSC on nanostructured surfaces functionalized with laminin-521 enhances Hgf expression in HSC, demonstrating that these ECM proteins are critically involved in HSC function. During aging, HSC acquire a senescence-associated secretory phenotype and lower their growth factor expression essential for tissue repair. Our findings suggest that impaired mechanosensing via integrin α 5 /β 1 in HSC contributes to age-related reduction of ECM and HGF release that could affect liver regeneration. K E Y W O R D S aging, hepatic stellate cells, integrins, laminins, mechanobiology S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Impaired integrin α₅/β₁‐mediated hepatocyte growth factor release by stellate cells of the aged liver

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

A Hydrogel Platform that Incorporates Laminin Isoforms for Efficient Presentation of Growth Factors – Neural Growth and Osteogenesis

Dobre

Oliva

Ciccone

et al. 2021

Adv Funct Materials

View full text Add to dashboard Cite

Laminins (LMs) are important structural proteins of the extracellular matrix (ECM). The abundance of every LM isoform is tissue-dependent, suggesting that LM has tissue-specific roles. LM binds growth factors (GFs), which are powerful cytokines widely used in tissue engineering due to their ability to control stem cell differentiation. Currently, the most commonly used ECM mimetic material in vitro is Matrigel, a matrix of undefined composition containing LM and various GFs, but subjected to batch variability and lacking control of physicochemical properties. Inspired by Matrigel, a new and completely defined hydrogel platform based on hybrid LM-poly(ethylene glycol) (PEG) hydrogels with controllable stiffness (1-25 kPa) and degradability is proposed. Different LM isoforms are used to bind and efficiently display GFs (here, bone morphogenetic protein (BMP-2) and beta-nerve growth factor (β-NGF)), enabling their solid-phase presentation at ultralow doses to specifically target a range of tissues. The potential of this platform to trigger stem cell differentiation toward osteogenic lineages and stimulate neural cells growth in 3D, is demonstrated. These hydrogels enable 3D, synthetic, defined composition, and reproducible cell culture microenvironments reflecting the complexity of the native ECM, where GFs in combination with LM isoforms yield the full diversity of cellular processes.

show abstract

Cancer stem cells: Masters of all traits

Leck,

Abd El-Aziz,

McKelvey

et al. 2025

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

Laminin-521 promotes quiescence in isolated stellate cells from rat liver

Cited by 16 publications

References 57 publications

Impaired integrin α₅/β₁‐mediated hepatocyte growth factor release by stellate cells of the aged liver

Impaired integrin α₅/β₁‐mediated hepatocyte growth factor release by stellate cells of the aged liver

A Hydrogel Platform that Incorporates Laminin Isoforms for Efficient Presentation of Growth Factors – Neural Growth and Osteogenesis

Cancer stem cells: Masters of all traits

Contact Info

Product

Resources

About

Laminin-521 promotes quiescence in isolated stellate cells from rat liver

Cited by 16 publications

References 57 publications

Impaired integrin α5/β1‐mediated hepatocyte growth factor release by stellate cells of the aged liver

Impaired integrin α5/β1‐mediated hepatocyte growth factor release by stellate cells of the aged liver

A Hydrogel Platform that Incorporates Laminin Isoforms for Efficient Presentation of Growth Factors – Neural Growth and Osteogenesis

Cancer stem cells: Masters of all traits

Contact Info

Product

Resources

About

Impaired integrin α₅/β₁‐mediated hepatocyte growth factor release by stellate cells of the aged liver

Impaired integrin α₅/β₁‐mediated hepatocyte growth factor release by stellate cells of the aged liver