Antifibrotic Activity of Acylated and Unacylated Ghrelin

Abstract

Fibrosis can affect almost all tissues and organs, it often represents the terminal stage of chronic diseases, and it is regarded as a major health issue for which efficient therapies are needed. Tissue injury, by inducing necrosis/apoptosis, triggers inflammatory response that, in turn, promotes fibroblast activation and pathological deposition of extracellular matrix. Acylated and unacylated ghrelin are the main products of the ghrelin gene. The acylated form, through its receptor GHSR-1a, stimulates appetite and growth hormone (GH) release. Although unacylated ghrelin does not bind or activate GHSR-1a, it shares with the acylated form several biological activities. Ghrelin peptides exhibit anti-inflammatory, antioxidative, and antiapoptotic activities, suggesting that they might represent an efficient approach to prevent or reduce fibrosis. The aim of this review is to summarize the available evidence regarding the effects of acylated and unacylated ghrelin on different pathologies and experimental models in which fibrosis is a predominant characteristic.

Ghrelin accelerates wound healing in combined radiation and wound injury in mice

“…This phenomenon was unexpected previously for ghrelin that can stimulate GH secretion and promote cell proliferation . However, ghrelin has been also reported to possess antifibrotic property . Otherwise, in another in vitro experiment, we found that ghrelin decreased the proliferative activity of HaCaT epidemic cells instead of improving it (data not shown); however, ghrelin increased the cell viability of irradiated HaCaT epidemic cells in a dose‐dependent manner (data not shown).…”

“…In chronic liver injury and fibrogenesis, ghrelin was reported to mitigate liver injury and inhibit fibrogenesis by NO release . In other studies, ghrelin was also proved to be an antifibrotic reagent partly by reducing collagen production through the inhibition of TGF‐β signalling pathway . However, our study indicated that ghrelin promoted NO and TGF‐β synthesis and collagen formation in the early stage of wound healing in CRWI mice.…”

Hexarelin treatment preserves myocardial function and reduces cardiac fibrosis in a mouse model of acute myocardial infarction

“…; Angelino et al. ). Interventions targeting excessive fibrosis as a result of MI are of major therapeutic importance in the treatment of HF (Samuel et al.…”

“…The GHS-R appears to mediate the action of HEX (Mao et al 2013(Mao et al , 2014a. The antifibrotic effects of GHS have been investigated with promising results in various models of cardiac injury such as doxorubicin cardiotoxicity isoproterenol administration, myocardial infarction, and spontaneous or diabetes-associated hypertension (Angelino et al 2015).…”

Polymorphism of regulatory region of GHRL gene (‐2531C>T) as a promising predictive factor for radiotherapy‐induced oral mucositis in patients with head neck cancer

“…What is more, ghrelin modifies the function of fibroblasts and reduces their production of collagen. Indirectly, by limiting the penetration of inflammatory cells into the damaged tissue and reducing the release of cytokines responsible for fibroblast activation and directly, by blocking the TGF‐β signaling pathway . Another mechanism responsible for the influence of ghrelin on the healing process, as it was demonstrated in a study by Kwan et al, is the reduction of microvascular leaks during inflammation through the GHS‐R1a‐mediated NF‐κB pathway.…”