B-cell lymphoma/leukaemia 10 and angiotensin II-induced kidney injury. Issue 5 (26th June 2019)

• Record Type: Journal Article
• Authors: Markó, Lajos; Park, Joon-Keun; Henke, Norbert; Rong, Song; Balogh, András; Klamer, Samuel; Bartolomaeus, Hendrik; Wilck, Nicola; Ruland, Jürgen; Forslund, Sofia K; Luft, Friedrich C; Dechend, Ralf; Müller, Dominik N
• Is Part Of: Cardiovascular research. Volume 116:Issue 5(2020)
• Page Start: 1059
• Page End: 1070
• Publication Date: 2019-06-26
• Subjects: Angiotensin II -- Bcl10 -- Kidney -- Podocyte -- Albuminuria; Cardiovascular system -- Diseases -- Periodicals; Cardiovascular system -- Periodicals; 616.1
• DOI: 10.1093/cvr/cvz169
• Languages: English
• ISSNs: 0008-6363

Abstract

Abstract: Aims: B-cell lymphoma/leukaemia 10 (Bcl10) is a member of the CARMA-Bcl10-MALT1 signalosome, linking angiotensin (Ang) II, and antigen-dependent immune-cell activation to nuclear factor kappa-B signalling. We showed earlier that Bcl10 plays a role in Ang II-induced cardiac fibrosis and remodelling, independent of blood pressure. We now investigated the role of Bcl10 in Ang II-induced renal damage. Methods and results: Bcl10 knockout mice (Bcl10 KO) and wild-type (WT) controls were given 1% NaCl in the drinking water and Ang II (1.44 mg/kg/day) for 14 days. Additionally, Bcl10 KO or WT kidneys were transplanted onto WT mice that were challenged by the same protocol for 7 days. Kidneys of Ang II-treated Bcl10 KO mice developed less fibrosis and showed fewer infiltrating cells. Nevertheless, neutrophil gelatinase-associated lipocalin ( Ngal ) and kidney injury molecule ( Kim ) 1 expression was higher in the kidneys of Ang II-treated Bcl10 KO mice, indicating exacerbated tubular damage. Furthermore, albuminuria was significantly higher in Ang II-treated Bcl10 KO mice accompanied by reduced glomerular nephrin expression and podocyte number. Ang II-treated WT mice transplanted with Bcl10 KO kidney showed more albuminuria and renal Ngal, compared to WT- > WT kidney-transplanted mice, as well as lower podocyte number but similar fibrosis and cell infiltration. Interestingly, mice lacking Bcl10 in the kidney exhibited less Ang II-induced cardiac hypertrophy than controls. Conclusion: Bcl10 has multi-faceted actions in Ang II-induced renal damage. On the one hand, global Bcl10 deficiency ameliorates renal fibrosis and cell infiltration; on the other hand, lack of renal Bcl10 aggravates albuminuria and podocyte damage. These data suggest that Bcl10 maintains podocyte integrity and renal function. Graphical Abstract: