Activation of silent mating type information regulation 2 homolog 1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and inflammation

Steinmetz, C. H.; Kashyap, Anubha; Zhivkova, Nataliya; Alizor, H; Ernst, Isabell; Gottfried-Brand, D; Janssen, Henning; Teufel, Andreas; Schulze‐Bergkamen, Henning; Lotz, Johannes; Kuball, Jürgen; Theobald, Matthias; Heise, Michael; Lang, Hauke; Galle, Peter R.; Strand, Dennis; Strand, Susanne

doi:10.1002/hep.29072

Cited by 8 publications

(8 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Silent information regulator 2 homolog1 (SIRT1), a NAD-dependent histone deacetylase, is involved in the pathogenesis of cancer [ 24 ], metabolic disease [ 25 ], inflammation [ 26 ] and arthritis [ 27 ]. The roles of SIRT1 in RA are mainly focused on the immune response [ 4 – 6 ], the proliferation and adhesion of RA FLSs [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

SIRT1 promotes tumor-like invasion of fibroblast-like synoviocytes in rheumatoid arthritis via targeting TIMP1

et al. 2017

View full text Add to dashboard Cite

Suppression of tissue inhibitor of matrix metalloproteinase (TIMP) is associated with the tumor-like invasion of fibroblast-like synoviocytes (FLSs) that occurs during rheumatoid arthritis-related cartilage destruction. Silent information regulator 2 homolog1 (SIRT1), a histone deacetylase, is widely involved in transcriptional regulation, genomic stability, metabolism and DNA repair. Recent studies suggest that SIRT1 may also impact inflammatory response and the proliferation of FLSs in rheumatoid arthritis (RA). However, it is unknown whether SIRT1 has a role in the tumor-like invasion of FLSs in rheumatoid arthritis. Herein we report that SIRT1 contributes to FLS invasion and cartilage destruction via a TIMP1-dependent mechanism. Elevated SIRT1 in RA synovia suppresses TIMP1 expression via deacetylation of TIMP1-associated histones, thereby disrupting the binding of the transcription factor specificity protein 1 (Sp1) to the TIMP1 promoter. In rats with collagen-induced arthritis, depletion of SIRT1 remarkably promoted TIMP1 expression in synovial tissues and ameliorated cartilage destruction. These results describe a new role for SIRT1 and demonstrate its potential value as a therapeutic target for rheumatoid arthritis.

show abstract

Section: Discussionmentioning

confidence: 99%

SIRT1 promotes tumor-like invasion of fibroblast-like synoviocytes in rheumatoid arthritis via targeting TIMP1

et al. 2017

View full text Add to dashboard Cite

show abstract

“… 701 Interestingly, pregnancy induces a state of immune tolerance, which can lead to spontaneous improvement of clinical symptoms of autoimmune hepatitis. 702 As for mechanism, this may be associated with the activation of SIRT1 by chorionic gonadotropin signaling. 702 Moreover, SIRT1, SIRT3, and SIRT6 may play important roles in cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

“… 702 As for mechanism, this may be associated with the activation of SIRT1 by chorionic gonadotropin signaling. 702 Moreover, SIRT1, SIRT3, and SIRT6 may play important roles in cirrhosis. 665 , 669 , 703 The study suggested that SIRT1 and SIRT6 were decreased at protein level in the livers of patients with cirrhosis.…”

Section: Introductionmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

213

View full text Add to dashboard Cite

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

show abstract

“…BALB/c mice with acute liver injury induced by anti-Fas antibody (Jo 2) and agonistic CD95-antibodieshad significantly reduced levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) when also treated with hCG. Mice treated with hCG also showed less CD4 + T cell infiltration and fewer apoptotic hepatocytes, confirming the effectiveness of hCG as an anti-inflammatory agent (90).…”

Section: Tempering Inflammation With Hcgmentioning

confidence: 60%

Human Chorionic Gonadotropin and Related Peptides: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis

et al. 2021

View full text Add to dashboard Cite

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources (“cytokine storm”). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.

show abstract

Activation of silent mating type information regulation 2 homolog 1 by human chorionic gonadotropin exerts a therapeutic effect on hepatic injury and inflammation

Cited by 8 publications

References 51 publications

SIRT1 promotes tumor-like invasion of fibroblast-like synoviocytes in rheumatoid arthritis via targeting TIMP1

SIRT1 promotes tumor-like invasion of fibroblast-like synoviocytes in rheumatoid arthritis via targeting TIMP1

The sirtuin family in health and disease

Human Chorionic Gonadotropin and Related Peptides: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis

Contact Info

Product

Resources

About