Gene Expression for Extracellular Matrix Proteins in Shockwave-Induced Osteogenesis in Rats

2004 ◽  
Vol 74 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Kenji Takahashi ◽  
Masashi Yamazaki ◽  
Takashi Saisu ◽  
Arata Nakajima ◽  
Sumito Shimizu ◽  
...  
2001 ◽  
Vol 12 (11) ◽  
pp. 2300-2309 ◽  
Author(s):  
CHRISTIAN MORATH ◽  
CLAUDIUS DECHOW ◽  
INGO LEHRKE ◽  
VOLKER HAXSEN ◽  
RÜDIGER WALDHERR ◽  
...  

Abstract. Transforming growth factor—β1 (TGF-β1) overexpression plays a key role in the glomerular accumulation of extracellular matrix proteins in renal disease. Retinoids have previously been shown to significantly limit glomerular damage in rat experimental glomerulonephritis. Therefore, the effects of all-trans retinoic acid and isotretinoin on the components of the TGF-β system and extracellular matrix proteins in anti-Thy1.1-nephritis (Thy-GN) were investigated. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin (n= 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8),i.e., starting before or after induction of Thy-GN, respectively. Urinary TGF-β1 excretion was 60% lower in all-trans retinoic acid-treated animals with Thy-GN (P< 0.025). The increase of cortical TGF-β1 gene expression in Thy-GN rats was significantly attenuated with all-trans retinoic acid and even more with isotretinoin treatment as compared with untreated animals (P< 0.025). Cortical expression of TGF receptor II, but not receptor I gene expression, was significantly lower in animals treated with all-trans retinoic acid or isotretinoin (P< 0.05). In all-trans retinoic acid—treated animals with Thy-GN, the increase of glomerular TGF-β1 protein (P< 0.008) and TGF-β1 (P< 0.025) and TGF receptor II mRNA (P< 0.015) was significantly less. Immunohistochemistry revealed less glomerular staining for TGF-β1 and TGF receptor II in the presence of all-trans retinoic acid. TGF-β1 immunostaining was not restricted to monocytes and macrophages, as indicated by double-staining. Glomerular staining for collagen IV and collagen III was less in animals treated with isotretinoin (P< 0.02 for both) in contrast to all-trans retinoic acid, whereas fibronectin remained unchanged. It was concluded that the beneficial effects of retinoids on glomerular damage are presumably due to a marked reduction in renal TGF-β1 and TGF receptor II expression.


2017 ◽  
Vol 22 (1) ◽  
pp. 695-699 ◽  
Author(s):  
Radivojka Vulic ◽  
Silvia Tyciakova ◽  
Maria Dubrovcakova ◽  
Ludovit Skultety ◽  
Jan Lakota

2000 ◽  
Vol 105 (6) ◽  
pp. 2028-2038 ◽  
Author(s):  
Douglas S. Steinbrech ◽  
Babak J. Mehrara ◽  
Norman M. Rowe ◽  
Matthew E. Dudziak ◽  
Jonathan S. Luchs ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Sandrine Morel ◽  
Sabine Schilling ◽  
Mannekomba R. Diagbouga ◽  
Matteo Delucchi ◽  
Marie-Luce Bochaton-Piallat ◽  
...  

Background: Intracranial aneurysms (IAs) result from abnormal enlargement of the arterial lumen. IAs are mostly quiescent and asymptomatic, but their rupture leads to severe brain damage or death. As the evolution of IAs is hard to predict and intricates medical decision, it is essential to improve our understanding of their pathophysiology. Wall shear stress (WSS) is proposed to influence IA growth and rupture. In this study, we investigated the effects of low and supra-high aneurysmal WSS on endothelial cells (ECs).Methods: Porcine arterial ECs were exposed for 48 h to defined levels of shear stress (2, 30, or 80 dyne/cm2) using an Ibidi flow apparatus. Immunostaining for CD31 or γ-cytoplasmic actin was performed to outline cell borders or to determine cell architecture. Geometry measurements (cell orientation, area, circularity and aspect ratio) were performed on confocal microscopy images. mRNA was extracted for RNAseq analysis.Results: ECs exposed to low or supra-high aneurysmal WSS were more circular and had a lower aspect ratio than cells exposed to physiological flow. Furthermore, they lost the alignment in the direction of flow observed under physiological conditions. The effects of low WSS on differential gene expression were stronger than those of supra-high WSS. Gene set enrichment analysis highlighted that extracellular matrix proteins, cytoskeletal proteins and more particularly the actin protein family were among the protein classes the most affected by shear stress. Interestingly, most genes showed an opposite regulation under both types of aneurysmal WSS. Immunostainings for γ-cytoplasmic actin suggested a different organization of this cytoskeletal protein between ECs exposed to physiological and both types of aneurysmal WSS.Conclusion: Under both aneurysmal low and supra-high WSS the typical arterial EC morphology molds to a more spherical shape. Whereas low WSS down-regulates the expression of cytoskeletal-related proteins and up-regulates extracellular matrix proteins, supra-high WSS induces opposite changes in gene expression of these protein classes. The differential regulation in EC gene expression observed under various WSS translate into a different organization of the ECs’ architecture. This adaptation of ECs to different aneurysmal WSS conditions may affect vascular remodeling in IAs.


Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 92 ◽  
Author(s):  
Charles Malemud

An imbalance in gene expressional events skewing chondrocyte anabolic and catabolic pathways toward the latter causes an aberrant turnover and loss of extracellular matrix proteins in osteoarthritic (OA) articular cartilage. Thus, catabolism results in the elevated loss of extracellular matrix proteins. There is also evidence of an increase in the frequency of chondrocyte apoptosis that compromises the capacity of articular cartilage to undergo repair. Although much of the fundamental OA studies over the past 20 years identified and characterized many genes relevant to pro-inflammatory cytokines, apoptosis, and matrix metalloproteinases (MMPs)/a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS), more recent studies focused on epigenetic mechanisms and the associated role of microRNAs (miRs) in regulating gene expression in OA cartilage. Thus, several miRs were identified as regulators of chondrocyte signaling pathways, apoptosis, and proteinase gene expression. For example, the reduced expression of miR-146a was found to be coupled to reduced type II collagen (COL2) in OA cartilage, whereas MMP-13 levels were increased, suggesting an association between MMP-13 gene expression and COL2A1 gene expression. Results of these studies imply that microRNAs could become useful in the search for diagnostic biomarkers, as well as providing novel therapeutic targets for intervention in OA.


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