Histone Deacetylases in Vascular Pathophysiology: Regulation by Vasoactive Peptides and Growth Factors

HDAC4 (histone deacetylase 4) belongs to class IIa of histone deacetylases, which groups important regulators of gene expression, controlling pleiotropic cellular functions. Here we show that, in addition to the well-defined nuclear/cytoplasmic shuttling, HDAC4 activity is modulated by the ubiquitin–proteasome system. Serum starvation elicits the poly-ubiquitination and degradation of HDAC4 in nontransformed cells. Phosphorylation of serine 298 within the PEST1 sequence plays an important role in the control of HDAC4 stability. Serine 298 lies within a glycogen synthase kinase 3β consensus sequence, and removal of growth factors fails to trigger HDAC4 degradation in cells deficient in this kinase. GSK3β can phosphorylate HDAC4 in vitro, and phosphorylation of serine 302 seems to play the role of priming phosphate. We have also found that HDAC4 modulates random cell motility possibly through the regulation of KLF2 transcription. Apoptosis, autophagy, cell proliferation, and growth arrest were unaffected by HDAC4. Our data suggest a link between regulation of HDAC4 degradation and the control of cell motility as operated by growth factors.

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Amniotic Tissue Modulation of Knee Pain—A Focus on Osteoarthritis

The Journal of Knee Surgery ◽

10.1055/s-0038-1676370 ◽

2018 ◽

Vol 32 (01) ◽

pp. 026-036 ◽

Cited By ~ 1

Author(s):

Charles Hannon ◽

Adam Yanke ◽

Jack Farr

Keyword(s):

Clinical Trials ◽

Hyaluronic Acid ◽

Growth Factors ◽

Stromal Cells ◽

Level Of Evidence ◽

Vasoactive Peptides ◽

Biologic Effects ◽

Anti Inflammatory ◽

High Level ◽

Tissue Product

AbstractThe use of intra-articular therapies as sources of growth factors, anti-inflammatory mediators, and medicinal signaling cells for osteoarthritis (OA) is rapidly evolving. Amnion, chorion, amniotic fluid, and the umbilical cord are distinct placental tissues that have been investigated for use in OA. Amniotic membrane (AM) synthesizes a variety of growth factors, cytokines, and vasoactive peptides that modulate inflammation. In addition, they contain amniotic epithelial cells and amniotic mononuclear undifferentiated stromal cells, which have chondrogenic and osteogenic differentiation capacity. AMs are also rich sources of hyaluronic acid and proteoglycans, which could play a role in the potential therapeutic relief of OA. Currently, there are several commercially available formulations of AM that differ based on content as well as how they were preserved. Understanding the processing of amniotic tissue is important because of their distinct mechanical and biologic effects of preservation on AM grafts. To date, there have been two preclinical and only one clinical study on the use of AM for OA, which show promising results. Many high level of evidence clinical trials are currently underway investigating the use of AM of OA. Future basic science and clinical research is warranted to better understand the anti-inflammatory and chondroregenerative properties of amniotic tissue and to determine clinically what amniotic tissue product is most efficacious for symptomatic OA.

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Endothelins - vasoactive peptides and growth factors

Cell and Tissue Research ◽

10.1007/s004410051028 ◽

1998 ◽

Vol 292 (1) ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

Martin Stjernquist

Keyword(s):

Growth Factors ◽

Vasoactive Peptides

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Growth factors and the primary cilium in BALB/c 3T3 cells

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100128432 ◽

1987 ◽

Vol 45 ◽

pp. 830-831

Author(s):

R. W. Tucker ◽

N. S. More ◽

S. Jayaraman

Keyword(s):

Growth Factors ◽

Primary Cilium ◽

Cultured Cells ◽

Morphological Changes ◽

Calcium Ionophore ◽

Growth Stimulation ◽

Calcium Ionophore A23187 ◽

Ionophore A23187 ◽

3T3 Cells ◽

Microtubule Depolymerization

The mechanisms by which polypeptide growth factors Induce DNA synthesis in cultured cells is not understood, but morphological changes Induced by growth factors have been used as clues to Intracellular messengers responsible for growth stimulation. One such morphological change has been the transient disappearance of the primary cilium, a “9 + 0” cilium formed by the perinuclear centriole in interphase cells. Since calcium ionophore A23187 also produced both mitogenesis and ciliary changes, microtubule depolymerization might explain ciliary disappearance monitored by indirect immunofluorescence with anti-tubulin antibody. However, complete resorption and subsequent reformation of the primary cilium occurs at mitosis, and might also account for ciliary disappearance induced by growth factors. To settle this issue, we investigated the ultrastructure of the primary cilium using serial thin-section electron microscopy of quiescent BALB/c 3T3 cells before and after stimulation with serum.

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New insights into heparan sulphate biosynthesis from the study of mutant mice

Biochemical Society Symposium ◽

10.1042/bss0690047 ◽

2002 ◽

Vol 69 ◽

pp. 47-57 ◽

Cited By ~ 8

Author(s):

Catherine L. R. Merry ◽

John T. Gallagher

Keyword(s):

Growth Factors ◽

Biosynthetic Pathway ◽

Heparan Sulphate ◽

Mutant Mice ◽

Gene Products ◽

Multiple Gene ◽

Adhesion Proteins ◽

Ligand Interactions

Heparan sulphate (HS) is an essential co-receptor for a number of growth factors, morphogens and adhesion proteins. The biosynthetic modifications involved in the generation of a mature HS chain may determine the strength and outcome of HS–ligand interactions. These modifications are catalysed by a complex family of enzymes, some of which occur as multiple gene products. Various mutant mice have now been generated, which lack the function of isolated components of the HS biosynthetic pathway. In this discussion, we outline the key findings of these studies, and use them to put into context our own work concerning the structure of the HS generated by the Hs2st-/- mice.

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