Asgeirsdottir, S. A. and van Solingen, C. and Kurniati, N. F. and Zwiers, P. J. and Heeringa, P. and van Meurs, M. and Satchell, S. C. and Saleem, M. A. and Mathieson, P. W. and Banas, B. and Kamps, J. A. A. M. and Rabelink, T. J. and van Zonneveld, A. J. and Molema, G. (2012) MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 302 (12). F1630-F1639. ISSN 1931-857X, 1522-1466
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Asgeirsdottir SA, van Solingen C, Kurniati NF, Zwiers PJ, Heeringa P, van Meurs M, Satchell SC, Saleem MA, Mathieson PW, Banas B, Kamps JA, Rabelink TJ, van Zonneveld AJ, Molema G. MicroRNA-126 contributes to renal microvascular heterogeneity of VCAM-1 protein expression in acute inflammation. Am J Physiol Renal Physiol 302: F1630-F1639, 2012. First published March 14, 2012; doi: 10.1152/ajprenal.00400.2011.-Endothelial cells in different microvascular segments of the kidney have diverse functions and exhibit differential responsiveness to disease stimuli. The responsible molecular mechanisms are largely unknown. We previously showed that during hemorrhagic shock, VCAM-1 protein was expressed primarily in extraglomerular compartments of the kidney, while E-selectin protein was highly induced in glomeruli only (van Meurs M, Wulfert FM, Knol AJ, de Haes A, Houwertjes M, Aarts LPHJ, Molema G. Shock 29: 291-299, 2008). Here, we investigated the molecular control of expression of these endothelial cell adhesion molecules in mouse models of renal inflammation. Microvascular segment-specific responses to the induction of anti-glomerular basement membrane (anti-GBM), glomerulonephritis and systemic TNF-alpha treatment showed that E-selectin expression was transcriptionally regulated, with high E-selectin mRNA and protein levels preferentially expressed in the glomerular compartment. In contrast, VCAM-1 mRNA expression was increased in both arterioles and glomeruli, while VCAM-1 protein expression was limited in the glomeruli. These high VCAM-1 mRNA/low VCAM-1 protein levels were accompanied by high local microRNA (miR)-126 and Egfl7 levels, as well as higher Ets1 levels compared with arteriolar expression levels. Using miR-reporter constructs, the functional activity of miR-126 in glomerular endothelial cells could be demonstrated. Moreover, in vivo knockdown of miR-126 function unleashed VCAM-1 protein expression in the glomeruli upon inflammatory challenge. These data imply that miR-126 has a major role in the segmental, heterogenic response of renal microvascular endothelial cells to systemic inflammatory stimuli.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL-CELLS; IN-VIVO; VASCULAR INTEGRITY; ANGIOGENESIS; INHIBITION; MIR-126; KIDNEY; GENE; GLOMERULONEPHRITIS; RESPONSIVENESS; E-selectin; VCAM-1; glomeruli; arterioles; (post) transcriptional control |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 May 2020 04:48 |
| Last Modified: | 13 May 2020 04:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18630 |
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