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Transcriptomic profile and validation of the protective role of celecoxib on cirrhotic splenomegaly

ABSTRACT: Splenomegaly can exacerbate liver cirrhosis and portal hypertension. We have previously demonstrated that cyclooxygenase-2 (COX-2) inhibitor can attenuate cirrhotic splenomegaly. However, the mechanism of cirrhotic splenomegaly remains unclear and is the focus of this study. Material and methods: Intraperitoneal injection of thioacetamide (TAA) was used to induce cirrhotic splenomegaly. Thirty rats were randomized into the control group. TAA and TAA+Celecoxib groups. Splenic gene profiling was analyzed by high-throughput RNA sequencing. Histological analysis of spleen tissue was evaluated by H&E, Sirius red, Prussian blue staining, and transmission electron microscopy. The splenic mRNA levels of collagen III and α-SMA and splenic contents of Ki-67, VEGF, IL-6, and TNF- were quantified. Results: A total of 1461 differentially expressed genes (DEGs) were identified in the spleens of the TAA group compared to the control group. The immune response and immune cell activation might be the major signaling pathways involved in the pathogenesis of cirrhotic splenomegaly. With its immunoregulatory effect, celecoxib can ameliorate cirrhotic splenomegaly and liver cirrhosis. Furthermore, 304 coexisting DEGs were obtained between TAA vs. control and TAA+celecoxib vs. TAA. According to GO and KEGG analyses, celecoxib may attenuate cirrhotic splenomegaly by suppressing splenic immune cell proliferation, inflammation, immune regulation, and fibrogenesis. The impacts of celecoxib on splenic immune cell proliferation, inflammation, immune regulation, and extracellular matrix were then validated by the decreased splenic Ki-67-positive cells, macrophages, fibrotic areas, and mRNA levels of collagen III and α-SMA. Conclusions: Celecoxib attenuates cirrhotic splenomegaly by inhibiting splenic immune cell proliferation, inflammation, and fibrogenesis. The current study sheds light on the therapeutic strategy of liver cirrhosis by targeting splenic abnormalities and provides COX-2 inhibitors as a novel medical treatment for cirrhotic splenomegaly.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE216624 | GEO | 2025/09/28

REPOSITORIES: GEO

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Transcriptomic profile and validation of the protective role of celecoxib on cirrhotic splenomegaly

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