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Molecular insights ...
Molecular insights into the early stage of glomerular injury in IgA nephropathy using single-cell RNA sequencing
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- Zambrano, Sonia (author)
- Karolinska Univ, KI AZ Integrated Cardio Metab Ctr, Dept Lab Med, Div Pathol,Karolinska Inst,Hosp Huddinge, Blickagangen 6, S-14157 Stockholm, Sweden.
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- He, Liqun (author)
- Uppsala universitet,Vaskulärbiologi,Tianjin Med Univ, Gen Hosp, Dept Neurosurg, Tianjin Neurol Inst,Key Lab Postneuroinjury,Neuro, Tianjin, Peoples R China.
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- Kano, Toshiki (author)
- Juntendo Univ, Dept Nephrol, Fac Med, Tokyo, Japan.
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- Sun, Ying (author)
- Uppsala universitet,Vaskulärbiologi
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- Charrin, Emmanuelle (author)
- Karolinska Institutet,Karolinska Univ, KI AZ Integrated Cardio Metab Ctr, Dept Lab Med, Div Pathol,Karolinska Inst,Hosp Huddinge, Blickagangen 6, S-14157 Stockholm, Sweden.
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- Lal, Mark (author)
- AstraZeneca, Biosci Renal, Cardiovasc Renal & Metab, BioPharmaceut R&D,Res & Early Dev, Gothenburg, Sweden.
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- Betsholtz, Christer (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge, Huddinge, Sweden.
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- Suzuki, Yusuke (author)
- Juntendo Univ, Dept Nephrol, Fac Med, Tokyo, Japan.
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- Patrakka, Jaakko (author)
- Karolinska Institutet,Karolinska Univ, KI AZ Integrated Cardio Metab Ctr, Dept Lab Med, Div Pathol,Karolinska Inst,Hosp Huddinge, Blickagangen 6, S-14157 Stockholm, Sweden.
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Karolinska Univ, KI AZ Integrated Cardio Metab Ctr, Dept Lab Med, Div Pathol,Karolinska Inst,Hosp Huddinge, Blickagangen 6, S-14157 Stockholm, Sweden Vaskulärbiologi (creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
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In: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 101:4, s. 752-765
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Subject headings
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- IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and defined by the presence of IgA-containing immune complexes in the mesangium that induce an inflammation leading to glomerulonephritis. Since we poorly understand early mechanisms of glomerular injury in IgAN we performed single-cell RNA sequencing (scRNA-seq) analysis of glomerulus-associated cells using SMARTseq2-technology at the early stage of IgAN in grouped ddY-mice. Cell-specific molecular signatures unraveled a key role of endothelial cells in the early pathogenesis of IgAN, especially in the recruitment and infiltration of immune cells. Mesangial and podocyte cells demonstrated less molecular changes. Several intraglomerular paracrine pathways were detected, such as mesangial cell-derived Slit3 potentially activating Roboreceptors in podocyte/endothelial cells. Surprisingly, proximal tubular cells were strongly affected at the early stage and potential glomerulo-tubular cell-cell crosstalk pathways were identified. Importantly, many of the cellular transcriptomic signatures identified in this well-established mouse model were also detected in published bulk transcriptomic data in human IgAN. Moreover, we validated the functionality of key cell-cell crosstalk pathways using cell culture models, such as the effect of the Slit-Robo signalling axis. Thus, our study provides important novel molecular insights into the pathogenesis of early IgAN-associated glomerulopathy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Urologi och njurmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Urology and Nephrology (hsv//eng)
Keyword
- glomerulus
- IgA nephropathy
- single-cell sequencing
Publication and Content Type
- ref (subject category)
- art (subject category)
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