Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues

Dense matrices impede interstitial cell migration and subsequent repair. We hypothesized that nuclear stiffness is a limiting factor in migration and posited that repair could be expedited by transiently decreasing nuclear stiffness. To test this, we interrogated the interstitial migratory capacity of adult meniscal cells through dense fibrous networks and adult tissue before and after nuclear softening via the application of a histone deacetylase inhibitor, Trichostatin A (TSA) or knockdown of the filamentous nuclear protein Lamin A/C. Our results show that transient softening of the nucleus improves migration through microporous membranes, electrospun fibrous matrices, and tissue sections and that nuclear properties and cell function recover after treatment. We also showed that biomaterial delivery of TSA promoted in vivo cellularization of scaffolds by endogenous cells. By addressing the inherent limitations to repair imposed by nuclear stiffness, this work defines a new strategy to promote the repair of damaged dense connective tissues.

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Cell-extracellular matrix interactions under in vivo conditions during interstitial cell migration in Hydra vulgaris

Development ◽

10.1242/dev.120.2.425 ◽

1994 ◽

Vol 120 (2) ◽

pp. 425-432 ◽

Cited By ~ 2

Author(s):

X. Zhang ◽

M.P. Sarras

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Synthetic Peptide ◽

Interstitial Cell ◽

Extracellular Matrix Components ◽

Matrix Interactions ◽

Apical Half ◽

Matrix Components ◽

Extracellular Matrix Interactions

Interstitial cell (I-cell) migration in hydra is essential for establishment of the regional cell differentiation pattern in the organism. All previous in vivo studies have indicated that cell migration in hydra is a result of cell-cell interactions and chemotaxic gradients. Recently, in vitro cell adhesion studies indicated that isolated nematocytes could bind to substrata coated with isolated hydra mesoglea, fibronectin and type IV collagen. Under these conditions, nematocytes could be observed to migrate on some of these extracellular matrix components. By modifying previously described hydra grafting techniques, two procedures were developed to test specifically the role of extracellular matrix components during in vivo I-cell migration in hydra. In one approach, the extracellular matrix structure of the apical half of the hydra graft was perturbed using beta-aminopropionitrile and beta-xyloside. In the second approach, grafts were treated with fibronectin, RGDS synthetic peptide and antibody to fibronectin after grafting was performed. In both cases, I-cell migration from the basal half to the apical half of the grafts was quantitatively analyzed. Statistical analysis indicated that beta-aminopropionitrile, fibronectin, RGDS synthetic peptide and antibody to fibronectin all were inhibitory to I-cell migration as compared to their respective controls. beta-xyloside treatment had no effect on interstitial cell migration. These results indicate the potential importance of cell-extracellular matrix interactions during in vivo I-cell migration in hydra.

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Faculty Opinions recommendation of Nuclear softening expedites interstitial cell migration in fibrous networks and dense connective tissues.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.738177660.793578068 ◽

2020 ◽

Author(s):

Ivan Martin

Keyword(s):

Cell Migration ◽

Interstitial Cell ◽

Connective Tissues

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Pulmonary vascular extraction and distribution of antipyrine with alveolar flooding

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.269.5.h1811 ◽

1995 ◽

Vol 269 (5) ◽

pp. H1811-H1819

Author(s):

W. O. Cua ◽

V. Bower ◽

C. Tice ◽

F. P. Chinard

Keyword(s):

Tritiated Water ◽

Indicator Dilution ◽

Limiting Factor ◽

Multiple Indicator Dilution ◽

Transit Times ◽

Before And After ◽

Multiple Indicator ◽

Dilution Experiments ◽

Orthogonal Distribution

Transport characteristics of antipyrine (AP), 22Na+, and tritiated water (THO) were assessed in dog lungs by multiple indicator-dilution experiments in vivo with anesthesia and in isolated perfused preparations before and after alveolar flooding. In controls, outflow patterns of AP and THO were nearly identical. In flooding, AP and THO patterns separated. THO upslopes decreased and mean (t) and modal (tmax) transit times increased as flooding increased; AP initial upslopes remained relatively unchanged but t increased, whereas tmax decreased. Patterns of 22Na+ were unchanged. The results indicate 22Na+ limitation at the endothelium, AP limitation only at the epithelium, and no THO limitation. A mathematical model is based on axial and orthogonal distribution of AP and THO. With alveolar flooding, diffusional distance may be a limiting factor in this distribution.

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ENDOCRINE TESTICULAR FUNCTION IN VIVO AND IN VITRO IN INFERTILE MEN

Acta Endocrinologica ◽

10.1530/acta.0.0900544 ◽

1979 ◽

Vol 90 (3) ◽

pp. 544-551 ◽

Cited By ~ 19

Author(s):

E. Nieschlag ◽

E. J. Wickings ◽

J. Mauss

Keyword(s):

Leydig Cell ◽

Cell Function ◽

Testicular Tissue ◽

Plasma Testosterone ◽

Cell Hyperplasia ◽

Testosterone Levels ◽

Infertile Men ◽

Before And After

ABSTRACT In order to detect any possible Leydig cell dysfunction associated with male infertility, the endocrine capacity of the testes was investigated in vivo and in vitro in 21 infertile men. Plasma testosterone was determined before and after 3 days of hCG stimulation. Testicular tissue obtained by bilateral biopsies was subjected to (1) histological examination, (2) determination of basal testosterone concentration and (3) incubation with hCG. Patients were grouped according to histology. In vitro basal and stimulated testicular testosterone was similar in patients with normal histology, Sertoli-cell-only syndrome and spermatogenic arrest. Tissue from patients with Leydig cell hyperplasia showed 3-fold higher basal testosterone levels and a greater response to hCG. All patients had plasma testosterone levels and responses to hCG in the normal range. There was no significant correlation between the data obtained in vivo and in vitro, indicating that testosterone determinations in peripheral blood do not necessarily reflect the intratesticular situation. There was no evidence for gross abnormality in Leydig cell function accompanying disturbed spermatogenesis.

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In vivo Imaging β-cell Function Reveals Two Waves of β-cell Maturation

10.1101/159673 ◽

2017 ◽

Author(s):

Jia Zhao ◽

Weijian Zong ◽

Yi Wu ◽

Jiayu Shen ◽

Dongzhou Gou ◽

...

Keyword(s):

Cell Function ◽

Light Sheet ◽

Cell Maturation ◽

Β Cells ◽

Β Cell ◽

New Strategy ◽

Β Cell Function ◽

Insulin Secreting Cells

AbstractThe insulin-secreting cells generated from stem cells in vitro are less glucose responsive than primary β-cells. To search for the missing ingredients that are needed for β-cell maturation, we have longitudinally monitored function of every β-cell in Tg (ins:Rcamp1.07) zebrafish embryos with a newly-invented two-photon light-sheet microscope. We have shown that β-cell maturation begins from the islet mantle and propagates to the islet core during the hatching period, coordinated by the islet vascularization. Lower concentration of glucose is optimal to initiate β-cell maturation, while increased glucose delivery to every cell through microcirculation is required for functional boosting of the β-cells. Both the initiation and the boosting of β-cell maturation demands activation of calcineurin/NFAT by glucose. Calcineurin activator combined with glucose promotes mouse neonatal β-cells cultured in vitro to mature to a functional state similar to adult β-cells, suggesting a new strategy for improving stem cell-derived β-like cell function in vitro.

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HDAC inhibition protects degenerating cone photoreceptors in vivo

10.1101/049742 ◽

2016 ◽

Author(s):

Dragana Trifunović ◽

Blanca Arango-Gonzalez ◽

Antonella Comitato ◽

Melanie Barth ◽

Ayse Sahaboglu ◽

...

Keyword(s):

Cell Death ◽

Trichostatin A ◽

Treatment Options ◽

Hdac Inhibition ◽

Neuroprotective Effects ◽

Histone Deacetylase Inhibitor Trichostatin ◽

New Treatment ◽

Future Therapy

AbstractRetinal diseases caused by cone photoreceptor cell death are devastating as the patients are experiencing loss of accurate and color vision. Understanding the mechanisms of cone cell death and the identification of key players therein could provide new treatment options. We studied the neuroprotective effects of a histone deacetylase inhibitor, Trichostatin A (TSA), in a mouse model of inherited, primary cone degeneration (cpfl1). We show that HDAC inhibition protects cones in vitro, in retinal explant cultures. More importantly, in vivo a single TSA injection increased cone survival for up to 10 days post-injection. In addition, the abnormal, incomplete cone migration pattern in the cpfl1 retina was significantly improved by HDAC inhibition. These findings suggest a crucial role for HDAC activity in primary cone degeneration and highlight a new avenue for future therapy developments for cone dystrophies and diseases associated with impaired cone migration.

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Functional alterations of rabbit erythrocytes induced by Loxosceles gaucho venom

Human & Experimental Toxicology ◽

10.1177/0960327107084070 ◽

2007 ◽

Vol 26 (10) ◽

pp. 817-821 ◽

Cited By ~ 4

Author(s):

Orlando Cesar de Oliveira Barretto ◽

Karina Soeiro Prestes ◽

Lorena Kessia Figueiredo Fonseca ◽

Paulo Augusto Achucarro Silveira

Keyword(s):

Cell Function ◽

Polyacrylamide Gel Electrophoresis ◽

Osmotic Fragility ◽

Intradermal Injection ◽

Membrane Function ◽

Before And After ◽

Brown Spider ◽

Region 10 ◽

And Function

Loxoscelism is the syndrome caused by the brown spider Loxosceles gaucho bite in humans. Its effect on erythrocytes has been studied in humans, rabbits, pigs and guinea pigs. In this study, the damage that the L gaucho spider venom causes to the structure and function of erythrocytes in vivo was investigated in rabbits. Before and after the rabbits were envenomed, membrane proteins were studied through polyacrylamide gel electrophoresis and membrane function was ascertained using the osmotic fragility test, together with the highly sensitive technique of ektacytometry. Six New Zealand rabbits were inoculated by intradermal injection into the dorsal region (10 μg of venom/kg of body weight in 0.2 mL of saline). Blood was collected at 24, 48, 72 and 120 h after inoculation. The membrane protein study did not reveal any alteration in their relative band concentrations, but the osmotic fragility test showed increased hemolysis in slightly hypotonic sodium chloride solutions (at 0.6 and 0.55%). In addition, the ektacytometer study revealed greater deformability to increasing shear stress on the order of 3—30 Pascals when compared with controls, showing that the L gaucho venom does in fact alter red cell function. Human & Experimental Toxicology (2007) 26 , 817— 821

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CR6-Interacting Factor 1 Interacts with Orphan Nuclear Receptor Nur77 and Inhibits Its Transactivation

Molecular Endocrinology ◽

10.1210/me.2004-0107 ◽

2005 ◽

Vol 19 (1) ◽

pp. 12-24 ◽

Cited By ~ 31

Author(s):

Ki Cheol Park ◽

Kwang-Hoon Song ◽

Hyo Kyun Chung ◽

Ho Kim ◽

Dong Wook Kim ◽

...

Keyword(s):

Cell Cycle ◽

Nuclear Receptor ◽

Promoter Activity ◽

Trichostatin A ◽

In Vivo Studies ◽

Orphan Nuclear Receptor ◽

Histone Deacetylase Inhibitor Trichostatin ◽

Responsive Element

Abstract CR6-interacting factor 1 (CRIF1) was recently identified as a nuclear protein that interacts with the Gadd45 (growth arrest and DNA damage inducible 45) family of proteins and participates in the regulation of the G1/S phase of the cell cycle. However, the nuclear action of CRIF1 is largely unknown. In this study, we demonstrate that CRIF1 acts as a novel coregulator of transactivation of the orphan nuclear receptor Nur77. Both in vitro and in vivo studies show that CRIF1 interacts with Nur77 via the Nur77 AB domain and that it dramatically inhibits the AB domain-mediated transactivation of Nur77. Transient transfection assays demonstrate that CRIF1 inhibits steroid receptor coactivator-2-mediated Nur77 transactivation, and silencing of endogenous CRIF1 by small interfering RNA relieves this repression. CRIF1 possesses intrinsic repressor activities that are not affected by the histone deacetylase inhibitor Trichostatin A. In addition, overexpression of CRIF1 inhibits TSH/protein kinase A-induced Nur-responsive element promoter activity. CRIF1 inhibited Nur77-dependent induction of E2F1 promoter activity, mRNA expression, and Nur77-mediated G1/S progression in cell cycle. These results suggest that CRIF1 acts as a repressor of the orphan nuclear receptor Nur77 by inhibiting AB domain-mediated transcriptional activity.

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