دورية أكاديمية
Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet.
العنوان: | Krüppel-like Factor 9 (KLF9) Suppresses Hepatocellular Carcinoma (HCC)-Promoting Oxidative Stress and Inflammation in Mice Fed High-Fat Diet. |
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المؤلفون: | Brown AR; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Alhallak I; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Simmen RCM; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Melnyk SB; Arkansas Children's Research Institute, Little Rock, AR 72202, USA., Heard-Lipsmeyer ME; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Montales MTE; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Habenicht D; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Van TT; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA., Simmen FA; Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.; The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. |
المصدر: | Cancers [Cancers (Basel)] 2022 Mar 29; Vol. 14 (7). Date of Electronic Publication: 2022 Mar 29. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101526829 Publication Model: Electronic Cited Medium: Print ISSN: 2072-6694 (Print) Linking ISSN: 20726694 NLM ISO Abbreviation: Cancers (Basel) Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI |
مستخلص: | Obesity, oxidative stress, and inflammation are risk factors for hepatocellular carcinoma (HCC). We examined, in mice, the effects of Krüppel-like factor 9 (KLF9) knockout on: adiposity, hepatic and systemic oxidative stress, and hepatic expression of pro-inflammatory and NOX/DUOX family genes, in a high-fat diet (HFD) context. Male and female Klf9 +/+ (wild type, WT) and Klf9 -/- (knockout, KO) mice were fed HFD (beginning at age 35 days) for 12 weeks, after which liver and adipose tissues were obtained, and serum adiponectin and leptin levels, liver fat content, and markers of oxidative stress evaluated. Klf9 -/- mice of either sex did not exhibit significant alterations in weight gain, adipocyte size, adipokine levels, or liver fat content when compared to WT counterparts. However, Klf9 -/- mice of both sexes had increased liver weight/size (hepatomegaly). This was accompanied by increased hepatic oxidative stress as indicated by decreased GSH/GSSG ratio and increased homocysteine, 3-nitrotyrosine, 3-chlorotyrosine, and 4HNE content. Decreased GSH to GSSG ratio and a trend toward increased homocysteine levels were observed in the corresponding Klf9 -/- mouse serum. Gene expression analysis showed a heightened pro-inflammatory state in livers from Klf9 -/- mice. KLF9 suppresses hepatic oxidative stress and inflammation, thus identifying potential mechanisms for KLF9 suppression of HCC and perhaps cancers of other tissues. |
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معلومات مُعتمدة: | F31CA165665 United States NH NIH HHS; R01CA136493 United States NH NIH HHS; U54TR001629 United States NH NIH HHS; F31 CA165665 United States CA NCI NIH HHS; R01 CA136493 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: 3-chlorotyrosine; 3-nitrotyrosine; HNE; IL6; KLF9; Krüppel-like factor 9; NOX-4; glutathione; hepatocellular carcinoma; liver; oxidative stress; pro-inflammatory |
تواريخ الأحداث: | Date Created: 20220412 Latest Revision: 20220506 |
رمز التحديث: | 20221213 |
مُعرف محوري في PubMed: | PMC8996893 |
DOI: | 10.3390/cancers14071737 |
PMID: | 35406507 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2072-6694 |
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DOI: | 10.3390/cancers14071737 |