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Review

The Agonists of Peroxisome Proliferator-Activated Receptor-γ for Liver Fibrosis

, ORCID Icon &
Pages 2619-2628 | Published online: 18 Jun 2021

References

  • KisselevaT, BrennerD. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol. 2020.
  • TrivediP, WangS, FriedmanSL. The Power of Plasticity-Metabolic Regulation of Hepatic Stellate Cells. Cell Metab. 2020.
  • IoannouGN. HCC surveillance after SVR in patients with F3/F4 fibrosis. J Hepatol. 2021;74(2):458–465.33303216
  • ArroyoV, AngeliP, MoreauR, et al. The systemic inflammation hypothesis: towards a new paradigm of acute decompensation and multiorgan failure in cirrhosis. J Hepatol. 2020.
  • HanX, WuY, YangQ, CaoG. Peroxisome proliferator-activated receptors in the pathogenesis and therapies of liver fibrosis. Pharmacol Ther. 2020;222:107791.33321113
  • WuL, LiJ, FengJ, et al. Crosstalk between PPARs and gut microbiota in NAFLD. Biomed Pharmacother. 2021;136:111255.33485064
  • Cordoba-ChaconJ. Loss of Hepatocyte-Specific PPARgamma Expression Ameliorates Early Events of Steatohepatitis in Mice Fed the Methionine and Choline-Deficient Diet. PPAR Res. 2020;2020:9735083.32411189
  • ZardiE, NavariniL, SambataroG, et al. Hepatic PPARs: their role in liver physiology, fibrosis and treatment. Curr Med Chem. 2013;20(27):3370–3396.23746272
  • StaelsB, RubenstrunkA, NoelB, et al. Hepatoprotective effects of the dual peroxisome proliferator-activated receptor alpha/delta agonist, GFT505, in rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Hepatology. 2013;58(6):1941–1952.23703580
  • MoW, WangC, LiJ, et al. Fucosterol Protects against Concanavalin A-Induced Acute Liver Injury: focus on P38 MAPK/NF-kappaB Pathway Activity. Gastroenterol Res Pract. 2018;2018:2824139.30116260
  • WuL, GuoC, WuJ. Therapeutic potential of PPARgamma natural agonists in liver diseases. J Cell Mol Med. 2020;24(5):2736–2748.32031298
  • XiangS, ChenK, XuL, WangT, GuoC. Bergenin Exerts Hepatoprotective Effects by Inhibiting the Release of Inflammatory Factors, Apoptosis and Autophagy via the PPAR-gamma Pathway. Drug Des Devel Ther. 2020;14:129–143.
  • IssemannI, GreenS. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature. 1990;347(6294):645–650.2129546
  • WagnerN, WagnerKD. The Role of PPARs in Disease. Cells. 2020;9:11.
  • ChristofidesA, KonstantinidouE, JaniC, BoussiotisV. The role of peroxisome proliferator-activated receptors (PPAR) in immune responses. Metabolism. 2020;154338.32791172
  • WagnerN, WagnerK. PPARs and Angiogenesis-Implications in Pathology. Int J Mol Sci. 2020;21:16.
  • LiuY, WangJ, LuoS, ZhanY, LuQ. The roles of PPARγ and its agonists in autoimmune diseases: a comprehensive review. J Autoimmun. 2020;113:102510.32622513
  • TrumperV, WittigI, HeidlerJ, RichterF, BruneB, von KnethenA. Redox Regulation of PPARgamma in Polarized Macrophages. PPAR Res. 2020;2020:8253831.32695149
  • YemchenkoYO, ShynkevychVI, IshcheikinKY, KaidashevIP. PPAR-Gamma Agonist Pioglitazone Reduced CD68+ but Not CD163+ Macrophage Dermal Infiltration in Obese Psoriatic Patients. PPAR Res. 2020;2020:4548012.32411188
  • YuS, XuH. Couple dynamics: pPARγ and its ligand partners. Structure. 2012;20(1):2–4.22244751
  • KytikovaOY, PerelmanJM, NovgorodtsevaTP, et al. Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma. PPAR Res. 2020;2020:8906968.32395125
  • StasilowiczA, TomalaA, PodolakI, Cielecka-PiontekJ. Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment. Int J Mol Sci. 2021;22:2.
  • ZhaoQ, FanY, ZhaoJ, GaoS, ZhaoZ, WangK. DNA methylation patterns of peroxisome proliferator-activated receptor gamma gene associated with liver fibrosis and inflammation in chronic hepatitis B. J Viral Hepat. 2013;20(6):430–437.23647960
  • MahdinlooS, KiaieS, AmiriA, HemmatiS, ValizadehH, Zakeri-MilaniP. Efficient drug and gene delivery to liver fibrosis: rationale, recent advances, and perspectives. Acta pharmaceutica Sinica B. 2020;10(7):1279–1293.32874828
  • BerumenJ, BaglieriJ, KisselevaT, MekeelK. Liver fibrosis: pathophysiology and clinical implications. Wiley Interdiscip Rev Syst Biol Med. 2020;e1499.32713091
  • NiXX, LiXY, WangQ, HuaJ. Regulation of peroxisome proliferator-activated receptor-gamma activity affects the hepatic stellate cell activation and the progression of NASH via TGF-beta1/Smad signaling pathway. J Physiol Biochem. 2020.
  • LiuX, XuJ, RosenthalS, et al. Identification of Lineage-Specific Transcription Factors That Prevent Activation of Hepatic Stellate Cells and Promote Fibrosis Resolution. Gastroenterology. 2020;158(6):1728–1744.31982409
  • QuinteroP, ArreseM. Nuclear control of inflammation and fibrosis in nonalcoholic steatohepatitis: therapeutic potential of dual peroxisome proliferator-activated receptor alpha/delta agonism. Hepatology. 2013;58(6):1881–1884.23787705
  • WangY, NakajimaT, GonzalezFJ, TanakaN. PPARs as Metabolic Regulators in the Liver: lessons from Liver-Specific PPAR-Null Mice. Int J Mol Sci. 2020;21:6.
  • WangZ, XuJP, ZhengYC, et al. Peroxisome proliferator-activated receptor gamma inhibits hepatic fibrosis in rats. Hepatobiliary Pancreat Dis Int. 2011;10(1):64–71.21269937
  • YavromS, ChenL, XiongS, WangJ, RippeRA, TsukamotoH. Peroxisome proliferator-activated receptor gamma suppresses proximal alpha1(I) collagen promoter via inhibition of p300-facilitated NF-I binding to DNA in hepatic stellate cells. J Biol Chem. 2005;280(49):40650–40659.16216869
  • YuJ, ZhangS, ChuES, et al. Peroxisome proliferator-activated receptors gamma reverses hepatic nutritional fibrosis in mice and suppresses activation of hepatic stellate cells in vitro. Int J Biochem Cell Biol. 2010;42(6):948–957.20156580
  • ZhangF, KongD, ChenL, et al. Peroxisome proliferator-activated receptor-γ interrupts angiogenic signal transduction by transrepression of platelet-derived growth factor-β receptor in hepatic stellate cells. J Cell Sci. 2014;127:305–314.24259663
  • ChiabottoG, PasquinoC, CamussiG, BrunoS. Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis. Front Cell Dev Biol. 2020;8:594794.33425900
  • SamuelD. Systemic inflammation and liver cirrhosis complications: driving or secondary event? How to square the circle? J Hepatol. 2021.
  • Ramos-TovarE, MurielP. Molecular Mechanisms That Link Oxidative Stress, Inflammation, and Fibrosis in the Liver. Antioxidants. 2020;9:12.
  • DallioM, SanginetoM, RomeoM, et al. Immunity as Cornerstone of Non-Alcoholic Fatty Liver Disease: the Contribution of Oxidative Stress in the Disease Progression. Int J Mol Sci. 2021;22(1):564.
  • ChhimwalJ, SharmaS, KulurkarP, PatialV. Crocin attenuates CCl4-induced liver fibrosis via PPAR-gamma mediated modulation of inflammation and fibrogenesis in rats. Hum Exp Toxicol. 2020;39(12):1639–1649.32633567
  • DengW, MengZ, SunA, YangZ. Pioglitazone suppresses inflammation and fibrosis in nonalcoholic fatty liver disease by down-regulating PDGF and TIMP-2: evidence from in vitro study. Cancer Biomarkers. 2017;20(4):411–415.28946547
  • KumarDP, CaffreyR, MarioneauxJ, et al. The PPAR alpha/gamma Agonist Saroglitazar Improves Insulin Resistance and Steatohepatitis in a Diet Induced Animal Model of Nonalcoholic Fatty Liver Disease. Sci Rep. 2020;10(1):9330.32518275
  • PlatkoK, LebeauPF, ByunJH, et al. GDF10 blocks hepatic PPARgamma activation to protect against diet-induced liver injury. Mol Metab. 2019;27:62–74.31288993
  • GanJ, ZhengSJ, MaoXR, LiJF. Invariant natural killer T cells: not to be ignored in liver disease. J Dig Dis. 2021.
  • Sepulveda-CrespoD, ResinoS, MartinezI. Strategies Targeting the Innate Immune Response for the Treatment of Hepatitis C Virus-Associated Liver Fibrosis. Drugs. 2021.
  • RhaMS, HanJW, KohJY, et al. Impaired antibacterial response of liver sinusoidal Vgamma9(+)Vdelta2(+) T cells in patients with chronic liver disease. Gut. 2021.
  • LiangQ, HuY, ZhangM, et al. The T Cell Receptor Immune Repertoire Protects the Liver From Reconsitution. Front Immunol. 2020;11:584979.33391261
  • ChristofidesA, KonstantinidouE, JaniC, BoussiotisVA. The role of peroxisome proliferator-activated receptors (PPAR) in immune responses. Metabolism. 2021;114:154338.32791172
  • SilveiraLS, BatatinhaHAP, CastoldiA, et al. Exercise rescues the immune response fine-tuned impaired by peroxisome proliferator-activated receptors gamma deletion in macrophages. J Cell Physiol. 2019;234(4):5241–5251.30238979
  • LefereS, PuengelT, HundertmarkJ, et al. Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages(). J Hepatol. 2020;73(4):757–770.32360434
  • ZhangF, LuY, ZhengS. Peroxisome proliferator-activated receptor-γ cross-regulation of signaling events implicated in liver fibrogenesis. Cell Signal. 2012;24(3):596–605.22108088
  • LiJ, GuoC, WuJ. 15-Deoxy--(12,14)-Prostaglandin J2 (15d-PGJ2), an Endogenous Ligand of PPAR-gamma: function and Mechanism. PPAR Res. 2019;2019:7242030.31467514
  • SukFM, ChenCH, LinSY, et al. 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibits fibrogenic response in human hepatoma cells. Toxicol Lett. 2009;187(1):22–27.19429239
  • HeJ, BaiK, HongB, ZhangF, ZhengS. Docosahexaenoic acid attenuates carbon tetrachloride-induced hepatic fibrosis in rats. Int Immunopharmacol. 2017;53:56–62.29035816
  • HeJ, HongB, BianM, et al. Docosahexaenoic acid inhibits hepatic stellate cell activation to attenuate liver fibrosis in a PPARγ-dependent manner. Int Immunopharmacol. 2019;75:105816.31437794
  • HeL, LiZ, ZhouD, et al. Galanin receptor 2 mediates antifibrogenic effects of galanin on hepatic stellate cells. Exp Ther Med. 2016;12(5):3375–3380.27882166
  • ZhouQ, GuanW, QiaoH, et al. GATA binding protein 2 mediates leptin inhibition of PPARγ1 expression in hepatic stellate cells and contributes to hepatic stellate cell activation. Biochim Biophys Acta. 2014;1842:2367–2377.25305367
  • WaiK, LiangY, ZhouL, et al. The protective effects of Acanthus ilicifolius alkaloid A and its derivatives on pro- and anti-inflammatory cytokines in rats with hepatic fibrosis. Biotechnol Appl Biochem. 2015;62(4):537–546.25204790
  • ZhouY, JiaX, WangG, WangX, LiuJ. PI-3 K/AKT and ERK signaling pathways mediate leptin-induced inhibition of PPARgamma gene expression in primary rat hepatic stellate cells. Mol Cell Biochem. 2009;325(1–2):131–139.19191008
  • GuanW, ChengF, WuH, et al. GATA binding protein 3 is correlated with leptin regulation of PPARγ1 in hepatic stellate cells. J Cell Mol Med. 2017;21(3):568–578.27709831
  • ParkJK, KiMR, LeeHR, et al. Vitamin C deficiency attenuates liver fibrosis by way of up-regulated peroxisome proliferator-activated receptor-gamma expression in senescence marker protein 30 knockout mice. Hepatology. 2010;51(5):1766–1777.20162732
  • MarraF, DeFrancoR, RobinoG, et al. Thiazolidinedione treatment inhibits bile duct proliferation and fibrosis in a rat model of chronic cholestasis. World J Gastroenterol. 2005;11(32):4931–4938.16124041
  • ChenH, HeYW, LiuWQ, ZhangJH. Rosiglitazone prevents murine hepatic fibrosis induced by Schistosoma japonicum. World J Gastroenterol. 2008;14(18):2905–2911.18473419
  • WeiZ, ZhaoD, ZhangY, et al. Rosiglitazone ameliorates bile duct ligation-induced liver fibrosis by down-regulating NF-kappaB-TNF-alpha signaling pathway in a PPARgamma-dependent manner. Biochem Biophys Res Commun. 2019;519(4):854–860.31561855
  • ZhiS, ChenS, LiY, LiJ, ZhengY, YuF. Rosiglitazone Inhibits Activation of Hepatic Stellate Cells via Up-Regulating Micro-RNA-124-3p to Alleviate Hepatic Fibrosis. Dig Dis Sci. 2019;64(6):1560–1570.30673982
  • MakledM, SharawyM, El-AwadyM. The dual PPAR-α/γ agonist saroglitazar ameliorates thioacetamide-induced liver fibrosis in rats through regulating leptin. Naunyn-Schmiedeberg’s arch pharmacol. 2019;392(12):1569–1576.31367862
  • TsaiH, LiT, HuangC, et al. Beneficial Effects of the Peroxisome Proliferator-Activated Receptor α/γ Agonist Aleglitazar on Progressive Hepatic and Splanchnic Abnormalities in Cirrhotic Rats with Portal Hypertension. Am J Pathol. 2018;188(7):1608–1624.29929914
  • YangL, StimpsonSA, ChenL, Wallace HarringtonW, RockeyDC. Effectiveness of the PPARgamma agonist, GW570, in liver fibrosis. Inflamm Res. 2010;59(12):1061–1071.20585829
  • PlanagumàA, ClàriaJ, MiquelR, et al. The selective cyclooxygenase-2 inhibitor SC-236 reduces liver fibrosis by mechanisms involving non-parenchymal cell apoptosis and PPARgamma activation. FASEB j. 2005;19(9):1120–1122.15876570
  • XuJ, FuY, ChenA. Activation of peroxisome proliferator-activated receptor-gamma contributes to the inhibitory effects of curcumin on rat hepatic stellate cell growth. Am J Physiol Gastrointest Liver Physiol. 2003;285(1):G20–30.12660143
  • ZhengS, ChenA. Activation of PPARgamma is required for curcumin to induce apoptosis and to inhibit the expression of extracellular matrix genes in hepatic stellate cells in vitro. Biochem J. 2004;384:149–157.15320868
  • ZhangF, ZhangZ, ChenL, et al. Curcumin attenuates angiogenesis in liver fibrosis and inhibits angiogenic properties of hepatic stellate cells. J Cell Mol Med. 2014;18(7):1392–1406.24779927
  • QiuJ, ZhouQ, ZhaiX, JiaX, ZhouY. Curcumin regulates delta-like homolog 1 expression in activated hepatic stellate cell. Eur J Pharmacol. 2014;728:9–15.24534491
  • ZhaiX, QiaoH, GuanW, et al. Curcumin regulates peroxisome proliferator-activated receptor-γ coactivator-1α expression by AMPK pathway in hepatic stellate cells in vitro. Eur J Pharmacol. 2015;746:56–62.25445048
  • QiaoH, HanH, HongD, RenZ, ChenY, ZhouC. Protective effects of baicalin on carbon tetrachloride induced liver injury by activating PPARgamma and inhibiting TGFbeta1. Pharm Biol. 2011;49(1):38–45.20687787
  • YangM, ChiangY, HigashiyamaR, et al. Rosmarinic acid and baicalin epigenetically derepress peroxisomal proliferator-activated receptor γ in hepatic stellate cells for their antifibrotic effect. Hepatology. 2012;55(4):1271–1281.22095555
  • GuoC, XuL, HeQ, LiangT, DuanX, LiR. Anti-fibrotic effects of puerarin on CCl4-induced hepatic fibrosis in rats possibly through the regulation of PPAR-γ expression and inhibition of PI3K/Akt pathway. Food Chem Toxicol. 2013;56:436–442.23500774
  • ZhangF, LuS, HeJ, et al. Ligand Activation of PPARγ by Ligustrazine Suppresses Pericyte Functions of Hepatic Stellate Cells via SMRT-Mediated Transrepression of HIF-1α. Theranostics. 2018;8(3):610–626.29344293
  • de SouzaI, MartinsL, de VasconcelosM, et al. Resveratrol Regulates the Quiescence-Like Induction of Activated Stellate Cells by Modulating the PPARγ/SIRT1 Ratio. J Cell Biochem. 2015;116(10):2304–2312.25833683
  • LiuQ, WangC, LiuZ, et al. Hydroxysafflor yellow A suppresses liver fibrosis induced by carbon tetrachloride with high-fat diet by regulating PPAR-γ/p38 MAPK signaling. Pharm Biol. 2014;52(9):1085–1093.24618007
  • EliasMB, OliveiraFL, GumaFCR, MartucciRB, BorojevicR, TeodoroAJ. Lycopene inhibits hepatic stellate cell activation and modulates cellular lipid storage and signaling. Food Funct. 2019;10(4):1974–1984.30889234
  • XiongK, ShiM, ZhangT, HanH. Protective effect of picroside I against hepatic fibrosis in mice via sphingolipid metabolism, bile acid biosynthesis, and PPAR signaling pathway. Biomed Pharmacother. 2020;131:110683.32942155
  • ZhengM, LiY, WangG, et al. Protective effect of cultured bear bile powder against dimethylnitrosamine-induced hepatic fibrosis in rats. Biomed Pharmacother. 2019;112:108701.30818137
  • ZhouJ, LiuX, ChenT, ChengG, CaiS. Preventive effect of ethanol extract from Chinese sumac fruits against tetrachloromethane-induced liver fibrosis in mice. Food Funct. 2020;11(8):7061–7072.32725034
  • MahmoudA, HozayenW, HasanI, ShabanE, Bin-JumahM. Umbelliferone Ameliorates CCl-Induced Liver Fibrosis in Rats by Upregulating PPARγ and Attenuating Oxidative Stress, Inflammation, and TGF-β1/Smad3 Signaling. Inflammation. 2019;42(3):1103–1116.30741365
  • ChengY, MaiJ, WangM, ChenG, PingJ. Antifibrotic effect of total flavonoids of Astmgali Radix on dimethylnitrosamine-induced liver cirrhosis in rats. Chin J Integr Med. 2017;23(1):48–54.27787720
  • LiJ, DaiW, XiaY, et al. Astaxanthin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cells via Inhibition of Nf-Kappab P65 and Wnt/Beta-Catenin in Vitro. Mar Drugs. 2015;13(10):6064–6081.26404320
  • LiJ, WangF, XiaY, et al. Astaxanthin Pretreatment Attenuates Hepatic Ischemia Reperfusion-Induced Apoptosis and Autophagy via the ROS/MAPK Pathway in Mice. Mar Drugs. 2015;13(6):3368–3387.26023842
  • LiX, ChenY, WuS, et al. microRNA-34a and microRNA-34c promote the activation of human hepatic stellate cells by targeting peroxisome proliferator-activated receptor γ. Mol Med Rep. 2015;11(2):1017–1024.25370690
  • ZhuD, LyuL, ShenP, et al. rSjP40 protein promotes PPARγ expression in LX-2 cells through microRNA-27b. FASEB j. 2018;32(9):4798–4803.29608331
  • HuangY, KuoH, YangY, WangF. MicroRNA-29a is a key regulon that regulates BRD4 and mitigates liver fibrosis in mice by inhibiting hepatic stellate cell activation. Int J Med Sci. 2019;16(2):212–220.30745801
  • TaoL, WuL, ZhangW, et al. Peroxisome proliferator-activated receptor γ inhibits hepatic stellate cell activation regulated by miR-942 in chronic hepatitis B liver fibrosis. Life Sci. 2020;253:117572.32201276
  • AttiaY, ElalkamyE, HammamO, MahmoudS, El-KhatibA. Telmisartan, an AT1 receptor blocker and a PPAR gamma activator, alleviates liver fibrosis induced experimentally by Schistosoma mansoni infection. Parasit Vectors. 2013;6:199.23829789
  • HasanH, Abdel-RafeiM, GalalS. Diosmin attenuates radiation-induced hepatic fibrosis by boosting PPAR-γ expression and hampering miR-17-5p-activated canonical Wnt-β-catenin signaling. Biochemistry Cell Biol. 2017;95(3):400–414.
  • KumarV, MundraV, MahatoR. Nanomedicines of Hedgehog inhibitor and PPAR-γ agonist for treating liver fibrosis. Pharm Res. 2014;31(5):1158–1169.24249038
  • ZhangF, KongD, LuY, ZhengS. Peroxisome proliferator-activated receptor-gamma as a therapeutic target for hepatic fibrosis: from bench to bedside. Cell Mol Life Sci. 2013;70(2):259–276.22699820