The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast Differentiation Article Swipe
Nicholas W. Chavkin
,
Soichi Sano
,
Ying Wang
,
Kosei Oshima
,
Hayato Ogawa
,
Keita Horitani
,
Miho Sano
,
Susan MacLauchlan
,
Anders R. Nelson
,
Karishma Setia
,
Tanvi Vippa
,
Yosuke Watanabe
,
Jeffrey J. Saucerman
,
Karen K. Hirschi
,
Noyan Gokce
,
Kenneth Walsh
·
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.02.433549
YOU?
·
· 2021
· Open Access
·
· DOI: https://doi.org/10.1101/2021.03.02.433549
Background A hallmark of heart failure is cardiac fibrosis, which results from the injury-induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early pro-inflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and Results The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction (TAC) surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after TAC surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2-KO mice displayed a pro-inflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, TAC surgery led to the death of all mice by day 6 that was associated with myocardial hyper-inflammation and vascular leakage. Conclusions Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.
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- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2021.03.02.433549
- https://www.biorxiv.org/content/biorxiv/early/2021/03/02/2021.03.02.433549.full.pdf
- OA Status
- green
- Cited By
- 1
- References
- 76
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W3135129792
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W3135129792Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1101/2021.03.02.433549Digital Object Identifier
- Title
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The Cell Surface Receptors Ror1/2 Control Cardiac Myofibroblast DifferentiationWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2021Year of publication
- Publication date
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2021-03-02Full publication date if available
- Authors
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Nicholas W. Chavkin, Soichi Sano, Ying Wang, Kosei Oshima, Hayato Ogawa, Keita Horitani, Miho Sano, Susan MacLauchlan, Anders R. Nelson, Karishma Setia, Tanvi Vippa, Yosuke Watanabe, Jeffrey J. Saucerman, Karen K. Hirschi, Noyan Gokce, Kenneth WalshList of authors in order
- Landing page
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https://doi.org/10.1101/2021.03.02.433549Publisher landing page
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https://www.biorxiv.org/content/biorxiv/early/2021/03/02/2021.03.02.433549.full.pdfDirect link to full text PDF
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://www.biorxiv.org/content/biorxiv/early/2021/03/02/2021.03.02.433549.full.pdfDirect OA link when available
- Concepts
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Myofibroblast, Cardiac fibrosis, Fibroblast, Cellular differentiation, Fibrosis, Cell biology, Cancer research, Extracellular matrix, Biology, Medicine, Pathology, Cell culture, Genetics, Biochemistry, GeneTop concepts (fields/topics) attached by OpenAlex
- Cited by
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1Total citation count in OpenAlex
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2024: 1Per-year citation counts (last 5 years)
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76Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works | https://openalex.org/W2132250523, https://openalex.org/W2040383667, https://openalex.org/W2608644283, https://openalex.org/W2482213414, https://openalex.org/W2105849179, https://openalex.org/W2401757307, https://openalex.org/W2098455751, https://openalex.org/W2064046486, https://openalex.org/W2949746255, https://openalex.org/W2909389152, https://openalex.org/W3027235456, https://openalex.org/W2924188812, https://openalex.org/W1970315050, https://openalex.org/W1963481639, https://openalex.org/W2041935553, https://openalex.org/W2026668241, https://openalex.org/W2055887625, https://openalex.org/W2062408444, https://openalex.org/W2048044207, https://openalex.org/W2146651952, https://openalex.org/W2602494391, https://openalex.org/W2643137007, https://openalex.org/W2787147590, https://openalex.org/W3049271086, https://openalex.org/W2770576214, https://openalex.org/W2807278075, https://openalex.org/W2210752542, https://openalex.org/W1975711182, https://openalex.org/W2742840256, https://openalex.org/W2599641104, https://openalex.org/W2027894846, https://openalex.org/W2160679726, https://openalex.org/W2081655794, https://openalex.org/W2517937763, https://openalex.org/W2165015044, https://openalex.org/W2509623821, https://openalex.org/W1569274710, https://openalex.org/W2590469161, https://openalex.org/W2083839493, https://openalex.org/W2141140780, https://openalex.org/W2075234503, https://openalex.org/W1969206533, https://openalex.org/W2955166257, https://openalex.org/W2005963114, https://openalex.org/W1560586627, https://openalex.org/W2323326409, https://openalex.org/W2620721366, https://openalex.org/W2060880575, https://openalex.org/W2079746034, https://openalex.org/W2303587096, https://openalex.org/W2985594208, https://openalex.org/W2791059232, https://openalex.org/W3006232468, https://openalex.org/W2285299655, https://openalex.org/W2073078807, https://openalex.org/W2944757554, https://openalex.org/W2648216475, https://openalex.org/W2996222203, https://openalex.org/W2272713913, https://openalex.org/W2018347789, https://openalex.org/W2165379056, https://openalex.org/W1967431414, https://openalex.org/W2036711492, https://openalex.org/W2908708438, https://openalex.org/W2750808153, https://openalex.org/W2049432938, https://openalex.org/W2766935322, https://openalex.org/W3004683268, https://openalex.org/W3002436408, https://openalex.org/W2767701190, https://openalex.org/W2092807552, https://openalex.org/W1518273993, https://openalex.org/W2900002398, https://openalex.org/W3020229374, https://openalex.org/W2770646430, https://openalex.org/W3012748365 |
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