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Article

Extracellular Matrix Analysis of Human Renal Arteries in Both Quiescent and Active Vascular State

1
Department of Nephrology and Hypertension, Division of Internal Medicine and Dermatology, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands
2
Center for Proteomics, Erasmus Medical Center, 3015 CN Rotterdam, The Netherlands
3
Department of Pathology, Erasmus University Medical Center, 3015 CN Rotterdam, The Netherlands
4
Department of Cell and Chemical Biology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
5
Experimental Cardiology, Department of Cardiology, Thorax center, Erasmus MC, University Medical Center Rotterdam, PO Box 2040, 3000 CA Rotterdam, The Netherlands
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(11), 3905; https://doi.org/10.3390/ijms21113905
Received: 4 May 2020 / Revised: 27 May 2020 / Accepted: 29 May 2020 / Published: 30 May 2020
(This article belongs to the Special Issue Extracellular Matrix in Development and Disease 2.0)
In vascular tissue engineering strategies, the addition of vascular-specific extracellular matrix (ECM) components may better mimic the in vivo microenvironment and potentially enhance cell–matrix interactions and subsequent tissue growth. For this purpose, the exact composition of the human vascular ECM first needs to be fully characterized. Most research has focused on characterizing ECM components in mature vascular tissue; however, the developing fetal ECM matches the active environment required in vascular tissue engineering more closely. Consequently, we characterized the ECM protein composition of active (fetal) and quiescent (mature) renal arteries using a proteome analysis of decellularized tissue. The obtained human fetal renal artery ECM proteome dataset contains higher levels of 15 ECM proteins versus the mature renal artery ECM proteome, whereas 16 ECM proteins showed higher levels in the mature tissue compared to fetal. Elastic ECM proteins EMILIN1 and FBN1 are significantly enriched in fetal renal arteries and are mainly produced by cells of mesenchymal origin. We functionally tested the role of EMILIN1 and FBN1 by anchoring the ECM secreted by vascular smooth muscle cells (SMCs) to glass coverslips. This ECM layer was depleted from either EMILIN1 or FBN1 by using siRNA targeting of the SMCs. Cultured endothelial cells (ECs) on this modified ECM layer showed alterations on the transcriptome level of multiple pathways, especially the Rho GTPase controlled pathways. However, no significant alterations in adhesion, migration or proliferation were observed when ECs were cultured on EMILIN1- or FNB1-deficient ECM. To conclude, the proteome analysis identified unique ECM proteins involved in the embryonic development of renal arteries. Alterations in transcriptome levels of ECs cultured on EMILIN1- or FBN1-deficient ECM showed that these candidate proteins could affect the endothelial (regenerative) response. View Full-Text
Keywords: extracellular matrix; proteomics; EMILIN1; FBN1; vasculature extracellular matrix; proteomics; EMILIN1; FBN1; vasculature
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MDPI and ACS Style

van Dijk, C.G.M.; Louzao-Martinez, L.; van Mulligen, E.; Boermans, B.; Demmers, J.A.A.; van den Bosch, T.P.P.; Goumans, M.-J.; Duncker, D.J.; Verhaar, M.C.; Cheng, C. Extracellular Matrix Analysis of Human Renal Arteries in Both Quiescent and Active Vascular State. Int. J. Mol. Sci. 2020, 21, 3905. https://doi.org/10.3390/ijms21113905

AMA Style

van Dijk CGM, Louzao-Martinez L, van Mulligen E, Boermans B, Demmers JAA, van den Bosch TPP, Goumans M-J, Duncker DJ, Verhaar MC, Cheng C. Extracellular Matrix Analysis of Human Renal Arteries in Both Quiescent and Active Vascular State. International Journal of Molecular Sciences. 2020; 21(11):3905. https://doi.org/10.3390/ijms21113905

Chicago/Turabian Style

van Dijk, Christian G.M., Laura Louzao-Martinez, Elise van Mulligen, Bart Boermans, Jeroen A.A. Demmers, Thierry P.P. van den Bosch, Marie-José Goumans, Dirk J. Duncker, Marianne C. Verhaar, and Caroline Cheng. 2020. "Extracellular Matrix Analysis of Human Renal Arteries in Both Quiescent and Active Vascular State" International Journal of Molecular Sciences 21, no. 11: 3905. https://doi.org/10.3390/ijms21113905

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