Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia

Stojsavljević-Shapeski, Sanja; Virović-Jukić, Lucija; Tomas, Davor; Duvnjak, Marko; Tomašić, Vedran; Hrabar, Davor; Kralj, Dominik; Budimir, Ivan; Baršić, Neven; Ljubičić, Neven

doi:10.4240/wjgs.v13.i12.1708

Cited by 4 publications

(2 citation statements)

References 35 publications

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“…It is noteworthy that the latest genome-wide association studies (GWAS) and Mendelian randomization (MR) analyses suggest a potential causal relationship between elevated plasma ghrelin levels and a reduced risk of GI cancer [100]. Additionally, recent studies have identified significantly higher expression of ghrelin and GHS-R in colorectal adenomas compared to that in surrounding tissues [101]. All told, further research is warranted to explore plasma ghrelin levels in the CRC population, along with their relationship to factors such as patient heterogeneity and tumor staging [102].…”

Section: Ghrelin and Colorectal Cancermentioning

confidence: 99%

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Wu,

Zhu,

Dou

et al. 2024

CIMB

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This review elucidates the critical role of ghrelin, a peptide hormone mainly synthesized in the stomach in various gastrointestinal (GI) diseases. Ghrelin participates in diverse biological functions ranging from appetite regulation to impacting autophagy and apoptosis. In sepsis, it reduces intestinal barrier damage by inhibiting inflammatory responses, enhancing GI blood flow, and modulating cellular processes like autophagy and apoptosis. Notably, in inflammatory bowel disease (IBD), serum ghrelin levels serve as markers for distinguishing between active and remission phases, underscoring its potential in IBD treatment. In gastric cancer, ghrelin acts as an early risk marker, and due to its significant role in increasing the proliferation and migration of gastric cancer cells, the ghrelin–GHS-R axis is poised to become a target for gastric cancer treatment. The role of ghrelin in colorectal cancer (CRC) remains controversial; however, ghrelin analogs have demonstrated substantial benefits in treating cachexia associated with CRC, highlighting the therapeutic potential of ghrelin. Nonetheless, the complex interplay between ghrelin’s protective and potential tumorigenic effects necessitates a cautious approach to its therapeutic application. In post-GI surgery scenarios, ghrelin and its analogs could be instrumental in enhancing recovery and reducing complications. This article accentuates ghrelin’s multifunctionality, shedding light on its influence on disease mechanisms, including inflammatory responses and cancer progression, and examines its therapeutic potential in GI surgeries and disorders, advocating for continued research in this evolving field.

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Section: Ghrelin and Colorectal Cancermentioning

confidence: 99%

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Wu,

Zhu,

Dou

et al. 2024

CIMB

View full text Add to dashboard Cite

show abstract

“…GHS-R1a expression was also widespread in all human tissue studied [ 92 ]. Notably, mRNA expression of ghrelin, both GHS-Rs (GHS-R1a and GHS-R1b), and GOAT is also detected in the normal colon and human liver [ 71 , 92 , 96 , 97 , 98 , 99 ]. GHS-R transcript expression was detected in human hepatocytes and activated hepatic stellate cells (HSCs), but not in quiescent HSCs [ 42 ].…”

Section: The Ghrelin System—general Overviewmentioning

confidence: 99%

Role of the Ghrelin System in Colitis and Hepatitis as Risk Factors for Inflammatory-Related Cancers

Kasprzak

Adamek

2022

IJMS

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It is not known exactly what leads to the development of colorectal cancer (CRC) and hepatocellular carcinoma (HCC), but there are specific risk factors that increase the probability of their occurrence. The unclear pathogenesis, too-late diagnosis, poor prognosis as a result of high recurrence and metastasis rates, and repeatedly ineffective therapy of both cancers continue to challenge both basic science and practical medicine. The ghrelin system, which is comprised of ghrelin and alternative peptides (e.g., obestatin), growth hormone secretagogue receptors (GHS-Rs), and ghrelin-O-acyl-transferase (GOAT), plays an important role in the physiology and pathology of the gastrointestinal (GI) tract. It promotes various physiological effects, including energy metabolism and amelioration of inflammation. The ghrelin system plays a role in the pathogenesis of inflammatory bowel diseases (IBDs), which are well known risk factors for the development of CRC, as well as inflammatory liver diseases which can trigger the development of HCC. Colitis-associated cancer serves as a prototype of inflammation-associated cancers. Little is known about the role of the ghrelin system in the mechanisms of transformation of chronic inflammation to low- and high-grade dysplasia, and, finally, to CRC. HCC is also associated with chronic inflammation and fibrosis arising from different etiologies, including alcoholic and nonalcoholic fatty liver diseases (NAFLD), and/or hepatitis B (HBV) and hepatitis C virus (HCV) infections. However, the exact role of ghrelin in the progression of the chronic inflammatory lesions into HCC is still unknown. The aim of this review is to summarize findings on the role of the ghrelin system in inflammatory bowel and liver diseases in order to better understand the impact of this system on the development of inflammatory-related cancers, namely CRC and HCC.

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Therapeutic potential of ghrelin/GOAT/GHSR system in gastrointestinal disorders

Ma,

Yan,

Wang

et al. 2024

Front. Nutr.

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Ghrelin, a peptide primarily secreted in the stomach, acts via the growth hormone secretagogue receptor (GHSR). It regulates several physiological processes, such as feeding behavior, energy homeostasis, glucose and lipid metabolism, cardiovascular function, bone formation, stress response, and learning. GHSR exhibits significant expression within the central nervous system. However, numerous murine studies indicate that ghrelin is limited in its ability to enter the brain from the bloodstream and is primarily confined to specific regions, such as arcuate nucleus (ARC) and median eminence (ME). Nevertheless, the central ghrelin system plays an essential role in regulating feeding behavior. Furthermore, the role of vagal afferent fibers in regulating the functions of ghrelin remains a major topic of discussion among researchers. In recent times, numerous studies have elucidated the substantial therapeutic potential of ghrelin in most gastrointestinal (GI) diseases. This has led to the development of numerous pharmaceutical agents that target the ghrelin system, some of which are currently under examination in clinical trials. Furthermore, ghrelin is speculated to serve as a promising biomarker for GI tumors, which indicates its potential use in tumor grade and stage evaluation. This review presents a summary of recent findings in research conducted on both animals and humans, highlighting the therapeutic properties of ghrelin system in GI disorders.

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Expression of adipokine ghrelin and ghrelin receptor in human colorectal adenoma and correlation with the grade of dysplasia

Cited by 4 publications

References 35 publications

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Ghrelin in Focus: Dissecting Its Critical Roles in Gastrointestinal Pathologies and Therapies

Role of the Ghrelin System in Colitis and Hepatitis as Risk Factors for Inflammatory-Related Cancers

Therapeutic potential of ghrelin/GOAT/GHSR system in gastrointestinal disorders

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