Deletion of Mcpip1 in Mcpip1fl/flAlbCre mice recapitulates the phenotype of human primary biliary cholangitis

Kotlinowski, Jerzy; Hutsch, Tomasz; Czyżyńska-Cichoń, Izabela; Wadowska, Marta; Pydyn, Natalia; Jasztal, Agnieszka; Kij, Agnieszka; Dobosz, Ewelina; Lech, Maciej; Miękus, Katarzyna; Pośpiech, Ewelina; Fu, Mingui; Jura, Jolanta; Kozieł, Joanna; Chłopicki, Stefan

doi:10.1016/j.bbadis.2021.166086

Cited by 12 publications

(7 citation statements)

References 39 publications

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“…2B, right panel, arrowheads), along with fibrosis in portal areas (Fig. S4 right panel, asterisk) reflecting most of the features of human primary biliary cholangitis (PBC) (presented and discussed in details in [23]).…”

Section: Resultsmentioning

confidence: 99%

“…Notably, our observations are in accordance with another study, demonstrating that the deletion of Mcpip1 in Mcpip1 fl/fl Alb Cre mice is asymptomatic, in terms of blood morphology, cytokines, and chemokines detected in plasma. Instead, it leads to a massive hyperplasia of cholangiocytes and the development of primary biliary cholangitis [23]. The important role of Mcpip1 in regulation of hepatic homeostasis was recently demonstrated by Sun and coworkers.…”

Section: Discussionmentioning

confidence: 99%

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Role of Mcpip1 in obesity‐induced hepatic steatosis as determined by myeloid and liver‐specific conditional knockouts

et al. 2021

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Role of Mcpip1 in obesity‐induced hepatic steatosis as determined by myeloid and liver‐specific conditional knockouts

et al. 2021

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“…For these reasons, we explored whether the immunomodulatory properties of MCPIP are relevant in the course of AKI and sterile inflammation. MCPIP1 is known to act as a negative regulator of LPS-induced macrophage activation [49] and MCPIP1 deficiency in myeloid cells can contribute to autoimmune and severe inflammatory responses [27,33,34,50], suggesting that MCPIP1 in macrophages and granulocytes orchestrates inflammation and immunity. Our study now confirmed that MCPIP1 negatively regulates sterile inflammation and, thereby, limits acute IRI-induced AKI.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-Specific MCPIP1/Regnase-1 Attenuates Kidney Ischemia-Reperfusion Injury by Shaping the Local Inflammatory Response and Tissue Regeneration

Ribeiro

Dobosz

Krill

et al. 2022

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Sterile inflammation either resolves the initial insult or leads to tissue damage. Kidney ischemia/reperfusion injury (IRI) is associated with neutrophilic infiltration, enhanced production of inflammatory mediators, accumulation of necrotic cells and tissue remodeling. Macrophage-dependent microenvironmental changes orchestrate many features of the immune response and tissue regeneration. The activation status of macrophages is influenced by extracellular signals, the duration and intensity of the stimulation, as well as various regulatory molecules. The role of macrophage-derived monocyte chemoattractant protein-induced protein 1 (MCPIP1), also known as Regnase-1, in kidney ischemia-reperfusion injury (IRI) and recovery from sterile inflammation remains unresolved. In this study, we showed that macrophage-specific Mcpip1 deletion significantly affects the kidney phenotype. Macrophage-specific Mcpip1 transgenic mice displayed enhanced inflammation and loss of the tubular compartment upon IRI. We showed that MCPIP1 modulates sterile inflammation by negative regulation of Irf4 expression and accumulation of IRF4+ cells in the tissue and, consequently, suppresses the post-ischemic kidney immune response. Thus, we identified MCPIP1 as an important molecular sentinel of immune homeostasis in experimental acute kidney injury (AKI) and renal fibrosis.

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“…Bile duct pathology in Mcpip1 fl/fl Alb Cre mice included hyperplasia of the intrahepatic bile ducts, bile duct epithelium disruption and fibrosis, resulting in lumen obstruction and bile duct destruction. The livers of these mice were characterized by granuloma formation and parenchymal inflammation with concomitant infiltration of lymphocytes (CD4 + and CD8 + ), macrophages and neutrophils [ 37 ].…”

Section: Transgenic Murine Models Of Primary Biliary Cholangitismentioning

confidence: 99%

Selected transgenic murine models of human autoimmune liver diseases

et al. 2022

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Murine models of human diseases are of outmost importance for both studying molecular mechanisms driving their development and testing new treatment strategies. In this review, we first discuss the etiology and risk factors for autoimmune liver disease, including primary biliary cholangitis, autoimmune hepatitis and primary sclerosing cholangitis. Second, we highlight important features of murine transgenic models that make them useful for basic scientists, drug developers and clinical researchers. Next, a brief description of each disease is followed by the characterization of selected animal models.

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Deletion of Mcpip1 in Mcpip1fl/flAlbCre mice recapitulates the phenotype of human primary biliary cholangitis

Cited by 12 publications

References 39 publications

Role of Mcpip1 in obesity‐induced hepatic steatosis as determined by myeloid and liver‐specific conditional knockouts

Role of Mcpip1 in obesity‐induced hepatic steatosis as determined by myeloid and liver‐specific conditional knockouts

Macrophage-Specific MCPIP1/Regnase-1 Attenuates Kidney Ischemia-Reperfusion Injury by Shaping the Local Inflammatory Response and Tissue Regeneration

Selected transgenic murine models of human autoimmune liver diseases

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