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Vanlandewijck, MichaelORCID iD iconorcid.org/0000-0002-0709-7808
Publications (10 of 14) Show all publications
van Kuijk, K., Kuppe, C., Betsholtz, C., Vanlandewijck, M., Kramann, R. & Sluimer, J. C. (2019). Heterogeneity and plasticity in healthy and atherosclerotic vasculature explored by single-cell sequencing. Cardiovascular Research, 115(12), 1705-1715
Open this publication in new window or tab >>Heterogeneity and plasticity in healthy and atherosclerotic vasculature explored by single-cell sequencing
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2019 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 115, no 12, p. 1705-1715Article, review/survey (Refereed) Published
Abstract [en]

Cellular characteristics and their adjustment to a state of disease have become more evident due to recent advances in imaging, fluorescent reporter mice, and whole genome RNA sequencing. The uncovered cellular heterogeneity and/or plasticity potentially complicates experimental studies and clinical applications, as markers derived from whole tissue 'bulk' sequencing is unable to yield a subtype transcriptome and specific markers. Here, we propose definitions on heterogeneity and plasticity, discuss current knowledge thereof in the vasculature and how this may be improved by single-cell sequencing (SCS). SCS is emerging as an emerging technique, enabling researchers to investigate different cell populations in more depth than ever before. Cell selection methods, e.g. flow assisted cell sorting, and the quantity of cells can influence the choice of SCS method. Smart-Seq2 offers sequencing of the complete mRNA molecule on a low quantity of cells, while Drop-seq is possible on large numbers of cells on a more superficial level. SCS has given more insight in heterogeneity in healthy vasculature, where it revealed that zonation is crucial in gene expression profiles among the anatomical axis. In diseased vasculature, this heterogeneity seems even more prominent with discovery of new immune subsets in atherosclerosis as proof. Vascular smooth muscle cells and mesenchymal cells also share these plastic characteristics with the ability to up-regulate markers linked to stem cells, such as Sca-1 or CD34. Current SCS studies show some limitations to the number of replicates, quantity of cells used, or the loss of spatial information. Bioinformatical tools could give some more insight in current datasets, making use of pseudo-time analysis or RNA velocity to investigate cell differentiation or polarization. In this review, we discuss the use of SCS in unravelling heterogeneity in the vasculature, its current limitations and promising future applications.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
Heterogeneity, Single-cell sequencing, Vasculature, Atherosclerosis
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-396467 (URN)10.1093/cvr/cvz185 (DOI)000491246600011 ()31350876 (PubMedID)
Funder
Swedish Research Council, 2015-00550Swedish Cancer Society, 150735Knut and Alice Wallenberg Foundation, 2015:0030German Research Foundation (DFG), SFB TRR219
Available from: 2019-11-14 Created: 2019-11-14 Last updated: 2019-11-14Bibliographically approved
Vanlandewijck, M., He, L., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., . . . Betsholtz, C. (2018). A molecular atlas of cell types and zonation in the brain vasculature. Nature, 554(7693), 475-480
Open this publication in new window or tab >>A molecular atlas of cell types and zonation in the brain vasculature
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2018 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 554, no 7693, p. 475-480Article in journal (Refereed) Published
Abstract [en]

Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-349342 (URN)10.1038/nature25739 (DOI)000425597400036 ()29443965 (PubMedID)
Funder
AstraZenecaSwedish Research Council, 2015-00550, K2014-64X-20097-09-5EU, European Research Council, AdG294556Swedish Cancer Society, 150735, CAN 2016/271Knut and Alice Wallenberg Foundation, 2015.0030The Swedish Brain Foundation
Available from: 2018-04-26 Created: 2018-04-26 Last updated: 2019-03-24Bibliographically approved
Loganathan, K., Salem Said, E., Winterrowd, E., Orebrand, M., He, L., Vanlandewijck, M., . . . Jeansson, M. (2018). Angiopoietin-1 deficiency increases renal capillary rarefaction and tubulointerstitial fibrosis in mice. PLoS ONE, 13(1), Article ID e0189433.
Open this publication in new window or tab >>Angiopoietin-1 deficiency increases renal capillary rarefaction and tubulointerstitial fibrosis in mice
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2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 1, article id e0189433Article in journal (Refereed) Published
Abstract [en]

Presence of tubulointerstitial fibrosis is predictive of progressive decline in kidney function, independent of its underlying cause. Injury to the renal microvasculature is a major factor in the progression of fibrosis and identification of factors that regulate endothelium in fibrosis is desirable as they might be candidate targets for treatment of kidney diseases. The current study investigates how loss of Angipoietin-1 (Angpt1), a ligand for endothelial tyrosine-kinase receptor Tek (also called Tie2), affects tubulointerstitial fibrosis and renal microvasculature. Inducible Angpt1 knockout mice were subjected to unilateral ureteral obstruction (UUO) to induce fibrosis, and kidneys were collected at different time points up to 10 days after obstruction. Staining for aSMA showed that Angpt1 deficient kidneys had significantly more fibrosis compared to wildtype mice 3, 6, and 10 days after UUO. Further investigation 3 days after UUO showed a significant increase of Col1a1 and vimentin in Angpt1 deficient mice, as well as increased gene expression of Tgfb1, Col1a1, Fn1, and CD44. Kidney injury molecule 1 (Kim1/Havcr1) was significantly more increased in Angpt1 deficient mice 1 and 3 days after UUO, suggesting a more severe injury early in the fibrotic process in Angpt1 deficient mice. Staining for endomucin showed that capillary rarefaction was evident 3 days after UUO and Angpt1 deficient mice had significantly less capillaries 6 and 10 days after UUO compared to UUO kidneys in wildtype mice. RNA sequencing revealed downregulation of several markers for endothelial cells 3 days after UUO, and that Angpt1 deficient mice had a further downregulation of Emcn, Plvap, Pecam1, Erg, and Tek. Our results suggest that loss of Angpt1 is central in capillary rarefaction and fibrogenesis and propose that manipulations to maintain Angpt1 levels may slow down fibrosis progression.

National Category
Basic Medicine
Identifiers
urn:nbn:se:uu:diva-339417 (URN)10.1371/journal.pone.0189433 (DOI)000419101600018 ()
Funder
Swedish Research Council, 2012-865Åke Wiberg FoundationMagnus Bergvall FoundationEU, European Research CouncilKnut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2018-01-18 Created: 2018-01-18 Last updated: 2018-02-28Bibliographically approved
Mäe, M. A., Li, T., Bertuzzi, G., Raschperger, E., Vanlandewijck, M., He, L., . . . Genove, G. (2018). Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier. Scientific Reports, 8, Article ID 17462.
Open this publication in new window or tab >>Prolonged systemic hyperglycemia does not cause pericyte loss and permeability at the mouse blood-brain barrier
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2018 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 17462Article in journal (Refereed) Published
Abstract [en]

Diabetes mellitus is associated with cognitive impairment and various central nervous system pathologies such as stroke, vascular dementia, or Alzheimer's disease. The exact pathophysiology of these conditions is poorly understood. Recent reports suggest that hyperglycemia causes cerebral microcirculation pathology and blood-brain barrier (BBB) dysfunction and leakage. The majority of these reports, however, are based on methods including in vitro BBB modeling or streptozotocininduced diabetes in rodents, opening questions regarding the translation of the in vitro findings to the in vivo situation, and possible direct effects of streptozotocin on the brain vasculature. Here we used a genetic mouse model of hyperglycemia (Ins2(AKITA)) to address whether prolonged systemic hyperglycemia induces BBB dysfunction and leakage. We applied a variety of methodologies to carefully evaluate BBB function and cellular integrity in vivo, including the quantification and visualization of specific tracers and evaluation of transcriptional and morphological changes in the BBB and its supporting cellular components. These experiments did neither reveal altered BBB permeability nor morphological changes of the brain vasculature in hyperglycemic mice. We conclude that prolonged hyperglycemia does not lead to BBB dysfunction, and thus the cognitive impairment observed in diabetes may have other causes.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-372388 (URN)10.1038/s41598-018-35576-0 (DOI)000451619100004 ()30498224 (PubMedID)
Funder
Swedish Research Council, 2015-00550EU, European Research Council, AdG294556Knut and Alice Wallenberg Foundation, 2015.0030Swedish Cancer Society, CAN-2016-0777Swedish Cancer Society, 150735
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
He, L., Vanlandewijck, M., Mäe, M. A., Andrae, J., Ando, K., Del Gaudio, F., . . . Betsholtz, C. (2018). Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types. Scientific Data, 5, Article ID 180160.
Open this publication in new window or tab >>Single-cell RNA sequencing of mouse brain and lung vascular and vessel-associated cell types
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2018 (English)In: Scientific Data, E-ISSN 2052-4463, Vol. 5, article id 180160Article in journal (Refereed) Published
Abstract [en]

Vascular diseases are major causes of death, yet our understanding of the cellular constituents of blood vessels, including how differences in their gene expression profiles create diversity in vascular structure and function, is limited. In this paper, we describe a single-cell RNA sequencing (scRNA-seq) dataset that defines vascular and vessel-associated cell types and subtypes in mouse brain and lung. The dataset contains 3,436 single cell transcriptomes from mouse brain, which formed 15 distinct clusters corresponding to cell (sub) types, and another 1,504 single cell transcriptomes from mouse lung, which formed 17 cell clusters. In order to allow user-friendly access to our data, we constructed a searchable database (http://betsholtzlab.org/VascularSingleCells/database.html). Our dataset constitutes a comprehensive molecular atlas of vascular and vessel-associated cell types in the mouse brain and lung, and as such provides a strong foundation for future studies of vascular development and diseases.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2018
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-364391 (URN)10.1038/sdata.2018.160 (DOI)000442285500001 ()30129931 (PubMedID)
Funder
Swedish Research Council, 2015-00550EU, European Research Council, AdG294556Knut and Alice Wallenberg Foundation, 2015.0030Swedish Research Council, K2014-64x-20097-09-5Swedish Cancer Society, 150735Swedish Cancer Society, CAN 2016/271The Swedish Brain Foundation
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2018-11-02 Created: 2018-11-02 Last updated: 2018-11-02Bibliographically approved
Vanlandewijck, M., Dadras, M. S., Lomnytska, M., Mahzabin, T., Lee Miller, M., Busch, C., . . . Moustakas, A. (2018). The protein kinase SIK downregulates the polarity protein Par3. OncoTarget, 9, 5716-5735
Open this publication in new window or tab >>The protein kinase SIK downregulates the polarity protein Par3
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2018 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 9, p. 5716-5735Article in journal (Refereed) Published
Abstract [en]

The multifunctional cytokine transforming growth factor β (TGFβ) controls homeostasis and disease during embryonic and adult life. TGFβ alters epithelial cell differentiation by inducing epithelial-mesenchymal transition (EMT), which involves downregulation of several cell-cell junctional constituents. Little is understood about the mechanism of tight junction disassembly by TGFβ. We found that one of the newly identified gene targets of TGFβ, encoding the serine/threonine kinase salt-inducible kinase 1 (SIK), controls tight junction dynamics. We provide bioinformatic and biochemical evidence that SIK can potentially phosphorylate the polarity complex protein Par3, an established regulator of tight junction assembly. SIK associates with Par3, and induces degradation of Par3 that can be prevented by proteasomal and lysosomal inhibition or by mutation of Ser885, a putative phosphorylation site on Par3. Functionally, this mechanism impacts on tight junction downregulation. Furthermore, SIK contributes to the loss of epithelial polarity and examination of advanced and invasive human cancers of diverse origin displayed high levels of SIK expression and a corresponding low expression of Par3 protein. High SIK mRNA expression also correlates with lower chance for survival in various carcinomas. In specific human breast cancer samples, aneuploidy of tumor cells best correlated with cytoplasmic SIK distribution, and SIK expression correlated with TGFβ/Smad signaling activity and low or undetectable expression of Par3. Our model suggests that SIK can act directly on the polarity protein Par3 to regulate tight junction assembly.

National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
urn:nbn:se:uu:diva-334429 (URN)10.18632/oncotarget.23788 (DOI)29464029 (PubMedID)
Note

Michael Vanlandewijck and Mahsa Shahidi Dadras contributed equally to this work.

Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2019-10-11Bibliographically approved
Carthy, J. M., Stoeter, M., Bellomo, C., Vanlandewijck, M., Heldin, A., Moren, A., . . . Moustakas, A. (2016). Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation. Scientific Reports, 6, Article ID 29868.
Open this publication in new window or tab >>Chemical regulators of epithelial plasticity reveal a nuclear receptor pathway controlling myofibroblast differentiation
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2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 29868Article in journal (Refereed) Published
Abstract [en]

Plasticity in epithelial tissues relates to processes of embryonic development, tissue fibrosis and cancer progression. Pharmacological modulation of epithelial transitions during disease progression may thus be clinically useful. Using human keratinocytes and a robotic high-content imaging platform, we screened for chemical compounds that reverse transforming growth factor beta (TGF-beta)-induced epithelial-mesenchymal transition. In addition to TGF-beta receptor kinase inhibitors, we identified small molecule epithelial plasticity modulators including a naturally occurring hydroxysterol agonist of the liver X receptors (LXRs), members of the nuclear receptor transcription factor family. Endogenous and synthetic LXR agonists tested in diverse cell models blocked alpha-smooth muscle actin expression, myofibroblast differentiation and function. Agonist-dependent LXR activity or LXR overexpression in the absence of ligand counteracted TGF-beta-mediated myofibroblast terminal differentiation and collagen contraction. The protective effect of LXR agonists against TGF-beta-induced pro-fibrotic activity raises the possibility that anti-lipidogenic therapy may be relevant in fibrotic disorders and advanced cancer.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-301020 (URN)10.1038/srep29868 (DOI)000379878300001 ()27430378 (PubMedID)
Funder
Swedish Cancer Society, CAN 2006/1078, CAN 2009/900, CAN 2012/438Swedish Research Council, K2007-66X-14936-04-3, K2010-67X-14936-07-3, K2013-66X-14936-10-5EU, FP7, Seventh Framework Programme
Available from: 2016-08-17 Created: 2016-08-17 Last updated: 2017-12-05Bibliographically approved
Vanlandewijck, M., Lebouvier, T., Mae, M. A., Nahar, K., Hornemann, S., Kenkel, D., . . . Betsholtz, C. (2015). Functional Characterization of Germline Mutations in PDGFB and PDGFRB in Primary Familial Brain Calcification. PLoS ONE, 10(11), Article ID e0143407.
Open this publication in new window or tab >>Functional Characterization of Germline Mutations in PDGFB and PDGFRB in Primary Familial Brain Calcification
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0143407Article in journal (Refereed) Published
Abstract [en]

Primary Familial Brain Calcification (PFBC), a neurodegenerative disease characterized by progressive pericapillary calcifications, has recently been linked to heterozygous mutations in PDGFB and PDGFRB genes. Here, we functionally analyzed several of these mutations in vitro. All six analyzed PDGFB mutations led to complete loss of PDGF-B function either through abolished protein synthesis or through defective binding and/or stimulation of PDGF-R beta. The three analyzed PDGFRB mutations had more diverse consequences. Whereas PDGF-R beta autophosphorylation was almost totally abolished in the PDGFRB L658P mutation, the two sporadic PDGFRB mutations R987W and E1071V caused reductions in protein levels and specific changes in the intensity and kinetics of PLC. activation, respectively. Since at least some of the PDGFB mutations were predicted to act through haploinsufficiency, we explored the consequences of reduced Pdgfb or Pdgfrb transcript and protein levels in mice. Heterozygous Pdgfb or Pdgfrb knockouts, as well as double Pdgfb(+/-); Pdgfrb(+/-) mice did not develop brain calcification, nor did Pdgfrb(redeye/redeye) mice, which show a 90% reduction of PDGFR beta protein levels. In contrast, Pdgfb(ret/ret) mice, which have altered tissue distribution of PDGF-B protein due to loss of a proteoglycan binding motif, developed brain calcifications. We also determined pericyte coverage in calcification-prone and non-calcification-prone brain regions in Pdgfb(ret/ret) mice. Surprisingly and contrary to our hypothesis, we found that the calcification-prone brain regions in Pdgfb(ret/ret) mice model had a higher pericyte coverage and a more intact blood-brain barrier (BBB) compared to non-calcification-prone brain regions. While our findings provide clear evidence that loss-of-function mutations in PDGFB or PDGFRB cause PFBC, they also demonstrate species differences in the threshold levels of PDGF-B/PDGF-R beta signaling that protect against small-vessel calcification in the brain. They further implicate region-specific susceptibility factor(s) in PFBC pathogenesis that are distinct from pericyte and BBB deficiency.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-272285 (URN)10.1371/journal.pone.0143407 (DOI)000365853900111 ()
Funder
EU, European Research CouncilSwedish Research CouncilSwedish Cancer SocietyKnut and Alice Wallenberg Foundation
Available from: 2016-01-15 Created: 2016-01-13 Last updated: 2019-03-24Bibliographically approved
Niaudet, C., Hofmann, J. J., Mae, M. A., Jung, B., Gängel, K., Vanlandewijck, M., . . . Betsholtz, C. (2015). Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium. PLoS ONE, 10(9), Article ID e0137949.
Open this publication in new window or tab >>Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0137949Article in journal (Refereed) Published
Abstract [en]

Despite its known expression in both the vascular endothelium and the lung epithelium, until recently the physiological role of the adhesion receptor Gpr116/ADGRF5 has remained elusive. We generated a new mouse model of constitutive Gpr116 inactivation, with a large genetic deletion encompassing exon 4 to exon 21 of the Gpr116 gene. This model allowed us to confirm recent results defining Gpr116 as necessary regulator of surfactant homeostasis. The loss of Gpr116 provokes an early accumulation of surfactant in the lungs, followed by a massive infiltration of macrophages, and eventually progresses into an emphysemalike pathology. Further analysis of this knockout model revealed cerebral vascular leakage, beginning at around 1.5 months of age. Additionally, endothelial-specific deletion of Gpr116 resulted in a significant increase of the brain vascular leakage. Mice devoid of Gpr116 developed an anatomically normal and largely functional vascular network, surprisingly exhibited an attenuated pathological retinal vascular response in a model of oxygen-induced retinopathy. These data suggest that Gpr116 modulates endothelial properties, a previously unappreciated function despite the pan-vascular expression of this receptor. Our results support the key pulmonary function of Gpr116 and describe a new role in the central nervous system vasculature.

National Category
Immunology in the medical area Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-265915 (URN)10.1371/journal.pone.0137949 (DOI)000361792100023 ()26394398 (PubMedID)
Funder
EU, European Research Council, 294556EU, European Research Council, ITN-2012-317250-VESSELSwedish Cancer SocietySwedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2015-11-04 Created: 2015-11-04 Last updated: 2018-04-07
Dahl, M., Maturi, V., Lönn, P., Papoutsoglou, P., Zieba, A., Vanlandewijck, M., . . . Moustakas, A. (2014). Fine-Tuning of Smad Protein Function by Poly(ADP-Ribose) Polymerases and Poly(ADP-Ribose) Glycohydrolase during Transforming Growth Factor β Signaling. PLoS ONE, 9(8), e103651
Open this publication in new window or tab >>Fine-Tuning of Smad Protein Function by Poly(ADP-Ribose) Polymerases and Poly(ADP-Ribose) Glycohydrolase during Transforming Growth Factor β Signaling
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, p. e103651-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Initiation, amplitude, duration and termination of transforming growth factor β (TGFβ) signaling via Smad proteins is regulated by post-translational modifications, including phosphorylation, ubiquitination and acetylation. We previously reported that ADP-ribosylation of Smads by poly(ADP-ribose) polymerase 1 (PARP-1) negatively influences Smad-mediated transcription. PARP-1 is known to functionally interact with PARP-2 in the nucleus and the enzyme poly(ADP-ribose) glycohydrolase (PARG) can remove poly(ADP-ribose) chains from target proteins. Here we aimed at analyzing possible cooperation between PARP-1, PARP-2 and PARG in regulation of TGFβ signaling.

METHODS:

A robust cell model of TGFβ signaling, i.e. human HaCaT keratinocytes, was used. Endogenous Smad3 ADP-ribosylation and protein complexes between Smads and PARPs were studied using proximity ligation assays and co-immunoprecipitation assays, which were complemented by in vitro ADP-ribosylation assays using recombinant proteins. Real-time RT-PCR analysis of mRNA levels and promoter-reporter assays provided quantitative analysis of gene expression in response to TGFβ stimulation and after genetic perturbations of PARP-1/-2 and PARG based on RNA interference.

RESULTS:

TGFβ signaling rapidly induces nuclear ADP-ribosylation of Smad3 that coincides with a relative enhancement of nuclear complexes of Smads with PARP-1 and PARP-2. Inversely, PARG interacts with Smads and can de-ADP-ribosylate Smad3 in vitro. PARP-1 and PARP-2 also form complexes with each other, and Smads interact and activate auto-ADP-ribosylation of both PARP-1 and PARP-2. PARP-2, similar to PARP-1, negatively regulates specific TGFβ target genes (fibronectin, Smad7) and Smad transcriptional responses, and PARG positively regulates these genes. Accordingly, inhibition of TGFβ-mediated transcription caused by silencing endogenous PARG expression could be relieved after simultaneous depletion of PARP-1.

CONCLUSION:

Nuclear Smad function is negatively regulated by PARP-1 that is assisted by PARP-2 and positively regulated by PARG during the course of TGFβ signaling.

National Category
Clinical Medicine
Identifiers
urn:nbn:se:uu:diva-231920 (URN)10.1371/journal.pone.0103651 (DOI)000341302700014 ()25133494 (PubMedID)
Available from: 2014-09-11 Created: 2014-09-11 Last updated: 2018-10-23Bibliographically approved
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ORCID iD: ORCID iD iconorcid.org/0000-0002-0709-7808

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