Contribution of the α8 Integrin Chain to the Expression of Extracellular Matrix Components

Volkert, Gudrun; Jahn, Angelika; Dinkel, Christina; Fahlbusch, Fabian; Zürn, Christina; Hilgers, Karl F.; Rascher, Wolfgang; Hartner, Andrea; Marek, Ines

doi:10.3109/15419061.2013.876012

Cited by 19 publications

(14 citation statements)

References 32 publications

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“…A nonsilencing siRNA (si co) (sense: UUC UCC GAA CGU GUC ACG UdT dT, antisense: ACG UGA CAC GUU CGG AGA AdTdT, Qiagen) was used as control. To control for effective silencing, real-time PCR for Itga8 expression levels was performed, as described in [26]. Moreover, western blot analysis was used to confirm down regulation of Itga8 on protein level.…”

Section: Methodsmentioning

confidence: 99%

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Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells

Marek¹,

Becker²,

Fahlbusch³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Healing of mesangioproliferative glomerulonephritis involves degradation of excess extracellular matrix, resolution of hypercellularity by apoptosis and phagocytosis of apoptotic cells. Integrin receptors participate in the regulation of phagocytosis. In mice deficient for alpha8 integrin (Itga8-/-) healing of glomerulonephritis is delayed. As Itga8 is abundant in mesangial cells (MC) which are non-professional phagocytes, we hypothesized that Itga8 facilitates phagocytosis of apoptotic cells and matrix components by MC. Methods: MC were isolated from wild type (WT) and Itga8-/- mice. Latex beads were coated with matrix components. Apoptosis was induced by cisplatin in macrophages and in DiI-stained MC. After coincubation of latex beads or apoptotic cells with MC, the phagocytosis rate was detected in WT and Itga8-/- MC via fluorescence microscopy and FACS analysis. Results: Itga8-/- MC showed reduced phagocytosis of matrix-coated beads and apoptotic cells compared to WT MC. Reduction of stress fibers was observed in Itga8-/- compared to WT MC. Inhibition of cytoskeletal reorganization by inhibition of Rac1 or ROCK during phagocytosis significantly decreased the rate of phagocytosis by WT MC but not by Itga8-/- MC. Conclusion: The expression of Itga8 facilitates phagocytosis in MC, likely mediated by Itga8-cytoskeleton interactions. An impairment of MC phagocytosis might thus contribute to a delayed glomerular regeneration in Itga8-/- mice.

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Section: Methodsmentioning

confidence: 99%

“…Rat MC were isolated from Sprague-Dawley rats as described in [26]. MC were grown in Dulbecco‘s modified Eagle’s Medium (DMEM with L-Glutamine; PAA Laboratories GmbH, Pasching, Austria) containing 10% FCS, 1% penicillin–streptomycin, 0.1% insulin (Sigma, Deisenhofen, Germany) in a 95% air – 5% CO 2 humidified atmosphere at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells

Marek¹,

Becker²,

Fahlbusch³

et al. 2018

Cell Physiol Biochem

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“…The mechanism by which Itga8 expression attenuates the development of tubulointerstitial fibrosis is still unclear. A direct effect of Itga8 expression on matrix turnover in several cell types could not be established [ 13 ]. Our own in vitro studies in glomerular mesangial cells, a cell type constitutively expressing Itga8 , additionally argue for a role for Itga8 signalling in regulating cell turnover: Expression of Itga8 attenuated proliferation and apoptosis in these cells [ 8 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Alpha8 Integrin (Itga8) Signalling Attenuates Chronic Renal Interstitial Fibrosis by Reducing Fibroblast Activation, Not by Interfering with Regulation of Cell Turnover

et al. 2016

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The α8 integrin (Itga8) chain contributes to the regulation of cell proliferation and apoptosis in renal glomerular cells. In unilateral ureteral obstruction Itga8 is de novo expressed in the tubulointerstitium and a deficiency of Itga8 results in more severe renal fibrosis after unilateral ureteral obstruction. We hypothesized that the increased tubulointerstitial damage after unilateral ureteral obstruction observed in mice deficient for Itga8 is associated with altered tubulointerstitial cell turnover and apoptotic mechanisms resulting from the lack of Itga8 in cells of the tubulointerstitium. Induction of unilateral ureteral obstruction was achieved by ligation of the right ureter in mice lacking Itga8. Unilateral ureteral obstruction increased proliferation and apoptosis rates of tubuloepithelial and interstitial cells, however, no differences were observed in the tubulointerstitium of mice lacking Itga8 and wild type controls regarding fibroblast or proliferating cell numbers as well as markers of endoplasmic reticulum stress and apoptosis after unilateral ureteral obstruction. In contrast, unilateral ureteral obstruction in mice lacking Itga8 led to more pronounced tubulointerstitial cell activation i.e. to the appearance of more phospho-SMAD2/3-positive cells and more α-smooth muscle actin-positive cells in the tubulointerstitium. Furthermore, a more severe macrophage and T-cell infiltration was observed in these animals compared to controls. Thus, Itga8 seems to attenuate tubulointerstitial fibrosis in unilateral ureteral obstruction not via regulation of cell turnover, but via regulation of TGF-β signalling, fibroblast activation and/or immune cell infiltration.

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“…Integrin α8 (ITGA8), an important component of ECM-receptor interaction pathway, played important roles in the expression of extracellular matrix components [ 47 ]. ITGA8 may participate in the degradation of extracellular matrix, including collagen type XI alpha 1, aggrecan, collagen type VI alpha 1 [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomic analysis of silica-induced pulmonary fibrosis in rats based on tandem mass tag (TMT) quantitation technology

Geng

Zhang

et al. 2020

PLoS ONE

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Silicosis is a systemic disease characterized by chronic persistent inflammation and incurable pulmonary fibrosis with the underlying molecular mechanisms to be fully elucidated. In this study, we employed tandem mass tag (TMT) based on quantitative proteomics technology to detect differentially expressed proteins (DEPs) in lung tissues of silica-exposed rats. A total of 285 DEPs (145 upregulated and 140 downregulated) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to predict the biological pathway and functional classification of the proteins. Results showed that these DEPs were mainly enriched in the phagosome, lysosome function, complement and the coagulation cascade, glutathione metabolism, focal adhesion and ECM-receptor interactions. To validate the proteomics data, we selected and analyzed the expression trends of six proteins including CD14, PSAP, GM2A, COL1A1, ITGA8 and CLDN5 using parallel reaction monitoring (PRM). The consistent result between PRM and TMT indicated the reliability of our proteomic data. These findings will help to reveal the pathogenesis of silicosis and provide potential therapeutic targets. Data are available via ProteomeXchange with identifier PXD020625 .

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Contribution of the α8 Integrin Chain to the Expression of Extracellular Matrix Components

Cited by 19 publications

References 32 publications

Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells

Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells

Alpha8 Integrin (Itga8) Signalling Attenuates Chronic Renal Interstitial Fibrosis by Reducing Fibroblast Activation, Not by Interfering with Regulation of Cell Turnover

Comparative proteomic analysis of silica-induced pulmonary fibrosis in rats based on tandem mass tag (TMT) quantitation technology

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