PPARGC1A affects inflammatory responses in photodynamic therapy (PDT)-treated inflammatory bowel disease (IBD)

Chao Liu; Yuhong Jiang; Ganglei Liu; Zhushu Guo; Qianqian Jin; Dongju Long; Weihan Zhou; Ke Qian; Hua Zhao; Kuijie Liu

doi:10.1016/j.bcp.2022.115119

PPARGC1A affects inflammatory responses in photodynamic therapy (PDT)-treated inflammatory bowel disease (IBD)

Biochem Pharmacol. 2022 Aug:202:115119. doi: 10.1016/j.bcp.2022.115119. Epub 2022 Jun 3.

Authors

Chao Liu¹, Yuhong Jiang¹, Ganglei Liu¹, Zhushu Guo¹, Qianqian Jin¹, Dongju Long¹, Weihan Zhou¹, Ke Qian¹, Hua Zhao¹, Kuijie Liu²

Affiliations

¹ Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha 410011, China.
² Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha 410011, China. Electronic address: liukuijie@csu.edu.cn.

PMID: 35667414
DOI: 10.1016/j.bcp.2022.115119

Abstract

Background: Chronic inflammation of the gastrointestinal tract is a feature of inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). Targeting inflammatory signaling represents promising strategy for IBD treatment regimens.

Methods: Dextran sulfate sodium (DSS)-induced colitis model was established in mice. Histopathological examinations were conducted by H&E staining and IHC staining. IL-1β, IL-10, and TNF-α were tested by ELISA kits. TargetScan was used to predict miRNAs that target PPARGC1A and luciferase activity assay was performed to validate the predicted binding.

Results: DSS-induced acute colitis model was successfully established in mice; photodynamic therapy (PDT) treatment partially improved DSS-induced colonic damages and cell inflammation. Microarray assays and integrative bioinformatics analysis identified PPARG coactivator 1 alpha (PPARGC1A) as a significantly differentially-expressed gene in PDT-treated IBD compared with non-treated IBD. PPARGC1A expression was downregulated in IBD clinical samples, DSS-induced colitis mice colons, and DSS-stimulated colonic epithelial cells, whereas partially upregulated by PDT treatment in DSS-stimulated cells. Single DSS stimulation significantly promoted cellular inflammation; PDT partially attenuated, whereas sh-PPARGC1A transduction further enhanced DSS effects on cancer cell inflammation. In colitis mice, DSS decreased PPRA-α and PPRA-γ proteins in mice colons; the in vivo effects of DSS were partially attenuated by PDT treatment, whereas amplified by sh-PPARGC1A transduction. Upstream miR-301a-3p targeted and inhibited PPARGC1A expression.

Conclusions: Collectively, PPARGC1A, which is downregulated in DSS-induced acute colitis and DSS-stimulated colonic epithelial cells, could be upregulated by PDT treatment. PPARGC1A knockdown could attenuate PDT therapeutic effects on DSS-induced acute colitis and DSS-stimulated colonic epithelial cells.

Keywords: Inflammation; Inflammatory bowel disease (IBD); PPARGC1A; Photodynamic therapy (PDT).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Colitis* / chemically induced
Colitis* / drug therapy
Colitis* / pathology
Colon / metabolism
Cytokines / metabolism
Dextran Sulfate / toxicity
Disease Models, Animal
Inflammation / metabolism
Inflammatory Bowel Diseases* / chemically induced
Inflammatory Bowel Diseases* / drug therapy
Inflammatory Bowel Diseases* / metabolism
Mice
Mice, Inbred C57BL
Photochemotherapy*

Substances

Cytokines
Dextran Sulfate