scholarly journals miR-29c induction contributes to downregulation of vascular extracellular matrix proteins by glucocorticoids

2015 ◽  
Vol 309 (2) ◽  
pp. C117-C125 ◽  
Author(s):  
Tsai-Der Chuang ◽  
William J. Pearce ◽  
Omid Khorram
Keyword(s):  
Collagen Type ◽  
Rat Aorta ◽  
Matrix Metalloproteinase 2 ◽  
Luciferase Reporter ◽  
Collagen Type Iv ◽  
Loss Of Function ◽  
Protein Levels ◽  
Maternal Undernutrition ◽  
Type Iv ◽  
Negative Controls

Maternal undernutrition increases maternal glucocorticoids (GCs) and alters microRNA expression in offspring. Given that the mechanisms of GC action on vascular development are not clear, this study examined the influence of GCs on microRNA 29c (miR-29c) and its predicted targets in primary rat aorta smooth muscle cells (RAOSMCs). Dexamethasone (Dex) and corticosterone (Cor) time-dependently increased miR-29c expression and reduced collagen type III (Col3A1), collagen type IV (Col4A5), elastin (ELN), and matrix metalloproteinase-2 (MMP2) protein in RAOSMCs. These effects were blocked by mifepristone. These genes were also targeted by miR-29c, as confirmed by a significant decrease in luciferase reporter activity of Col3A1 (34%), Col4A5 (45%), ELN (17%), and MMP2 (28%). In cells transfected with reporter plasmids, including the 3′-untranslated region of genes targeted by miR-29c, treatment with Dex or Cor also resulted in decreases in luciferase activity. Gain or loss of function of miR-29c significantly altered mRNA expression of Col3A1 (26% and 26%, respectively), Col4A5 (28% and 32%, respectively), and MMP2 (24% and 14%, respectively) but did not affect ELN. Gain or loss of function of miR-29c also significantly altered protein levels of Col3A1 (51% and 16%, respectively), Col4A5 (56% and 22%, respectively), ELN (53% and 71%, respectively), and MMP2 (28% and 53%, respectively). Coincubation of anti-miR-29c with Dex or Cor partially attenuated the effects of these steroids on protein expression of Col3A1 (25% and 24%, respectively), Col4A5 (26% and 44%, respectively), ELN (31% and 55%, respectively), and MMP2 (46% and 26%, respectively) in RAOSMCs compared with anti-miR negative controls. Our results demonstrate that GCs regulate the expression of Col3A1, Col4A5, ELN, and MMP2, at least in part, through induction of miR-29c.

BMP7 antagonizes TGF-β-dependent fibrogenesis in mesangial cells

2003 ◽  
Vol 284 (5) ◽  
pp. F1006-F1013 ◽  
Author(s):  
Shinong Wang ◽  
Raimund Hirschberg
Keyword(s):  
Growth Factor ◽  
Collagen Type ◽  
Mesangial Cells ◽  
Tissue Growth ◽  
Luciferase Reporter ◽  
Renal Diseases ◽  
Collagen Type Iv ◽  
Mrna Levels ◽  
Type Iv ◽  
Pai 1

Exogenous administration of recombinant human bone morphogenetic protein (BMP)-7 was recently shown to ameliorate renal glomerular and interstitial fibrosis in rodents with experimental renal diseases. We tested the hypothesis that BMP7 functions by antagonizing profibrogenic events that are induced by transforming growth factor (TGF)-β in cultured mesangial cells. Incubation of murine mesangial cells with TGF-β (50–200 pM) increased cell-associated collagen type IV and fibronectin, soluble collagen type IV, thrombospondin, and connective tissue growth factor (CTGF). Coincubation with recombinant human BMP7 (200 pM) reduced the increase of these ECM proteins and CTGF. The changes in collagen type IV and fibronectin proteins occurred without concomitant changes in collagen type α1IV and fibronectin mRNA levels, suggesting that TGF-β and BMP7 act primarily by affecting ECM protein degradation. Indeed, TGF-β decreases the levels and activity of matrix metalloprotease (MMP)-2, the major metalloprotease that is secreted by mesangial cells. Moreover, BMP7 inhibits TGF-β-induced activation of MMP2. Because TGF-β reduces the activity of MMPs through increasing plasminogen activator inhibitor (PAI)-1, we tested whether BMP7 interferes with this TGF-β effect. BMP7 reduces, by about two-thirds, the activation of a PAI-1 promoter/luciferase reporter in cells stably transfected with this construct. The findings from these studies indicate that BMP7 reduces TGF-β-induced ECM protein accumulation in cultured mesangial cells primarily by maintaining levels and activity of MMP2 partially through prevention of TGF-β-dependent upregulation of PAI-1.

Release of collagen type IV degrading activity from C6 astrocytoma cells and cell density

1996 ◽  
Vol 84 (6) ◽  
pp. 1013-1019 ◽  
Author(s):  
Masashi Tamaki ◽  
Warren McDonald ◽  
Rolando F. Del Maestro
Keyword(s):  
Cell Density ◽  
Collagen Type ◽  
Cell Communication ◽  
Collagen Type Iv ◽  
Major Protein ◽  
Content Type ◽  
Type Iv ◽  
Astrocytoma Cells ◽  
C6 Astrocytoma

✓ Type IV collagen is a major protein component of the vascular basement membrane and its degradation is crucial to the initiation of tumor-associated angiogenesis. The authors have investigated the influence of cell density on the release of collagen type IV degrading activity by C6 astrocytoma cells in monolayer culture. The release of collagen type IV degrading activity was assessed biochemically, immunocytochemically, and by Western blot analysis. The results demonstrate that increasing plating density and increasing cell density are associated with decreased collagen type IV degrading activity released per tumor cell. These findings indicate the existence of regulatory mechanisms dependent on cell—cell communication, which modulate release of collagen type IV degrading activity. The extrapolation of these results to the in vivo tumor microenvironment would suggest that individual and/or small groups of invading tumor cells, distant from the main tumor mass, would release substantial collagen type IV degrading activity, which may be crucial to their continued invasion and to angiogenesis.

Collagen type IV in acute rejection of kidney

2000 ◽  
Vol 32 (7) ◽  
pp. 1785 ◽  
Author(s):  
K Utsumi ◽  
T Sawada ◽  
E Adachi ◽  
S Horita ◽  
T Tojimbara ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Collagen Type ◽  
Collagen Type Iv ◽  
Type Iv

EOSINOPHILIC GASTRITIS IN CHILDREN: MORPHOLOGICAL AND IMMUNOHISTOCHEMICAL DIAGNOSTIC CRITERIA

2021 ◽  
Vol 74 (7) ◽  
pp. 1722-1727
Author(s):  
Vira I. Bobrova ◽  
Anastasia O. Horobets ◽  
Julia I. Proshchenko ◽  
Ludmila O. Levadna ◽  
Zoriana V. Selska
Keyword(s):  
Lamina Propria ◽  
Collagen Type ◽  
Morphological Changes ◽  
Prognostic Index ◽  
Lymphocytic Infiltration ◽  
Eosinophilic Infiltration ◽  
Nuclear Antigen ◽  
Collagen Type Iv ◽  
Eosinophilic Gastritis ◽  
Type Iv

The aim: To study peculiarities of morphological and immunohistochemical changes of stomach’s mucosa in eosinophilic gastritis in children Materials and methods: 64.1±6.0% patients with eosinophilic gastritis and 35.9±6.0% patients with lymphocytic gastritis participated in our investigation. In order to verify the diagnosis morphological and immunohistochemical diagnostics of the stomach’s mucosa was performed in all children. To assess morphological changes in tissues the specimens were colored with hematoxylin, eosin and picrofuchsin by van Gieson’s. Indirect streptavidin-peroxydase staining method was used for immunohistochemical investigation and the following indexes were assessed: proliferating cell nuclear antigen – PCNA, Bcl – 2, Вax, Collagen Type ІV, TGFβ and NF-κβ. Results: Comparative analysis of morphologic investigation has demonstrated that eosinophilic gastritis is characterized by fibrosis and fibroblasts proliferation into basal and superficial parts of mucosa’s lamina propria, multiple hemorrhages, thrombosis and erosions on the background of eosinophilic infiltration. Immunohistochemical indexes of cellular restoration in eosinophilic gastritis are characterized by increased proliferative activity and decreased indexes of proapoptotic and antiapoptotic activity. Prevalence of the reaction with the use of monoclonal antibodies to Collagen Type IV in majority of children with eosinophilic gastritis was characterized by separate fragmented foci in basal membranes of superficial epithelium. Remarkable TGFβ immune coloration was detected in majority of children on the background of fibrosis and eosinophilic infiltration of lamina propria. NF-κβ expression in epitheliocytes’ cytoplasm and nuclei was uneven. Homogenous remarkable coloration was detected in majority of patients with lymphocytic infiltration of mucosa. Conclusions: Eosinophilic gastritis course in children is characterized by remarkable inflammation, decreased regeneration of the mucosa, impairment of cellular restoration which is prognostic index of fibrous remodeling development.

Glycated albumin stimulation of PKC-β activity is linked to increased collagen IV in mesangial cells

1999 ◽  
Vol 276 (5) ◽  
pp. F684-F690 ◽  
Author(s):  
Margo P. Cohen ◽  
Fuad N. Ziyadeh ◽  
Gregory T. Lautenslager ◽  
Jonathan A. Cohen ◽  
Clyde W. Shearman
Keyword(s):  
Collagen Type ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Glycated Albumin ◽  
Matrix Proteins ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Pkc Β ◽  
Tgf Β1 ◽  
Stimulation Of

Albumin modified by Amadori-glucose adducts induces coordinate increases in the expression of extracellular matrix proteins, transforming growth factor (TGF)-β1, and the TGF-β type II receptor in glomerular mesangial cells. Because activation of protein kinase C (PKC) accompanies the increased mesangial cell expression of matrix proteins and TGF-β1 induced by high ambient glucose, we postulated that glycated albumin (GA) modulates PKC activity and that PKC participates in mediating the GA-induced stimulation of matrix production. To test this hypothesis, we examined the effects of PKC inhibitors on collagen type IV production by mouse or rat mesangial cells incubated with GA, and the influence of GA on PKC activity in these cells. Increased collagen type IV production evoked by GA in 5.5 and 25 mM glucose in mouse mesangial cells was prevented by both general (GF-109203X) and β-specific (LY-379196) PKC inhibitors. Total PKC activity, measured by phosphorylation of a PKC-specific substrate, increased with time after exposure of rat mesangial cells to GA compared with the nonglycated, glucose-free counterpart. GA caused an increase in PKC-β1 membrane-bound fraction and in total PKC activity in media containing physiological (5.5 mM) glucose concentrations in rat mesangial cells, confirming that the glucose-modified protein, and not a “hyperglycemic” milieu, was responsible. The findings indicate that Amadori-modified albumin stimulates mesangial cell PKC activity, and that activation of the PKC-β isoform is linked to the stimulation of collagen type IV production.

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