Antifibrotic and Anti-Inflammatory Actions of α-Melanocytic Hormone: New Roles for an Old Player

Dinparastisaleh, Roshan; Mirsaeidi, Mehdi

doi:10.3390/ph14010045

Cited by 19 publications

(42 citation statements)

References 186 publications

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“…The α-MSH, an endogenous neuropeptide derived from POMC, is widely expressed in various tissues and organs and plays an important role in a variety of biological processes, such as energy metabolism, body weight regulation, sexual activity, and exocrine secretion ( 39 ). This hormone also has broad anti-inflammatory effects ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

Serum levels of hormones regulating appetite in patients with cystic fibrosis − a single-center, cross-sectional study

et al. 2022

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Cystic fibrosis (CF), which is the most common inherited genetically determined disease caused by a mutation in the gene for the CF transmembrane conductance regulator protein. Pulmonary failure is the leading cause of death in this population, while the dysregulation of endocrine system creates significant disorders, including malnutrition, underweight, and CF-related diabetes. Therefore, the objective of our study was to determine the following hormones in the serum of patients with CF: ghrelin, putative peptide YY (PYY), Agouti-signaling protein (ASP), and alpha-melanocyte-stimulating hormone (α-MSH). To our knowledge, serum levels of PYY, ASP, and α-MSH have not yet been assessed in CF. For this purpose, we measured hormone levels using enzyme-linked immunosorbent assays in 38 patients from the local CF care center, as well as 16 sex- and age-matched healthy controls. Moreover, we estimated the correlations between the tested hormones and the parameters of the patients’ clinical status. In this study, we found sinificantly reduced serum levels of ghrelin and ASP in patients with CF (p<0.01). There was no difference in PYY and α-MSH levels between participants with CF and healthy subjects. Furthermore, there was no difference in hormone levels between females and males with CF. The type of gene mutation (homozygous or heterozygous for ΔF508) had no effect on hormone levels. Ghrelin was negatively correlated with age, body mass index, and C-reactive protein. PYY was negatively associated with the age of the patients. Hormone dysregulation in CF may contribute to decreased appetite, as well as many other disturbed processes. Therefore, ghrelin appears to play a key role in the regulation of energy management of CF. Future multicenter and multidisciplinary studies should focus on an unequivocal understanding of the role of these hormones in CF.

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Section: Discussionmentioning

confidence: 99%

Serum levels of hormones regulating appetite in patients with cystic fibrosis − a single-center, cross-sectional study

et al. 2022

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“…In dermal fibroblasts, α-MSH modulates collagen metabolism by improving the orientation of the collagen fibers [ 158 , 159 , 160 ]. α-MSH may drive the healing into a more regenerative/less scarring pathway by counteraction the pro-fibrotic action of TGFβ [ 160 , 161 ]. Recently, a higher prevalence of coarse collagen, pixel, and vessel density in photo-exposed areas has been associated with MC1R polymorphic variants [ 162 ].…”

Section: The Role Of Oxidative Stress In Chronological Senescence Of ...mentioning

confidence: 99%

Focus on the Contribution of Oxidative Stress in Skin Aging

et al. 2022

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Skin aging is one of the most evident signs of human aging. Modification of the skin during the life span is characterized by fine lines and wrinkling, loss of elasticity and volume, laxity, rough-textured appearance, and pallor. In contrast, photoaged skin is associated with uneven pigmentation (age spot) and is markedly wrinkled. At the cellular and molecular level, it consists of multiple interconnected processes based on biochemical reactions, genetic programs, and occurrence of external stimulation. The principal cellular perturbation in the skin driving senescence is the alteration of oxidative balance. In chronological aging, reactive oxygen species (ROS) are produced mainly through cellular oxidative metabolism during adenosine triphosphate (ATP) generation from glucose and mitochondrial dysfunction, whereas in extrinsic aging, loss of redox equilibrium is caused by environmental factors, such as ultraviolet radiation, pollution, cigarette smoking, and inadequate nutrition. During the aging process, oxidative stress is attributed to both augmented ROS production and reduced levels of enzymatic and non-enzymatic protectors. Apart from the evident appearance of structural change, throughout aging, the skin gradually loses its natural functional characteristics and regenerative potential. With aging, the skin immune system also undergoes functional senescence manifested as a reduced ability to counteract infections and augmented frequency of autoimmune and neoplastic diseases. This review proposes an update on the role of oxidative stress in the appearance of the clinical manifestation of skin aging, as well as of the molecular mechanisms that underline this natural phenomenon sometimes accelerated by external factors.

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“…α-MSH is also thought to inhibit NF-κB in T lymphocytes, leading to a decrease in IFN-γ production, whilst triggering upregulation of the anti-inflammatory cytokine IL-10 and Transforming growth factor (TGF)-β, possibly through cAMP responsive element binding protein (CREB). Thus, modulation of cAMP signaling by α-MSH can convert effector T lymphocytes into regulatory T lymphocytes ( 212 , 217 , 218 ). Furthermore, α-MSH was shown to also upregulate the production of IL-10 in macrophages and monocytes, which might assist the expansion of CM-initiating cells ( 216 , 219 ).…”

Section: The Role Of Melanin In Immune System Modulationmentioning

confidence: 99%

The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness

Cabaço

Tomás²,

Pojo³

et al. 2022

Front. Oncol.

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Skin cancers are among the most common cancers worldwide and are increasingly prevalent. Cutaneous melanoma (CM) is characterized by the malignant transformation of melanocytes in the epidermis. Although CM shows lower incidence than other skin cancers, it is the most aggressive and responsible for the vast majority of skin cancer-related deaths. Indeed, 75% of patients present with invasive or metastatic tumors, even after surgical excision. In CM, the photoprotective pigment melanin, which is produced by melanocytes, plays a central role in the pathology of the disease. Melanin absorbs ultraviolet radiation and scavenges reactive oxygen/nitrogen species (ROS/RNS) resulting from the radiation exposure. However, the scavenged ROS/RNS modify melanin and lead to the induction of signature DNA damage in CM cells, namely cyclobutane pyrimidine dimers, which are known to promote CM immortalization and carcinogenesis. Despite triggering the malignant transformation of melanocytes and promoting initial tumor growth, the presence of melanin inside CM cells is described to negatively regulate their invasiveness by increasing cell stiffness and reducing elasticity. Emerging evidence also indicates that melanin secreted from CM cells is required for the immunomodulation of tumor microenvironment. Indeed, melanin transforms dermal fibroblasts in cancer-associated fibroblasts, suppresses the immune system and promotes tumor angiogenesis, thus sustaining CM progression and metastasis. Here, we review the current knowledge on the role of melanin secretion in CM aggressiveness and the molecular machinery involved, as well as the impact in tumor microenvironment and immune responses. A better understanding of this role and the molecular players involved could enable the modulation of melanin secretion to become a therapeutic strategy to impair CM invasion and metastasis and, hence, reduce the burden of CM-associated deaths.

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Antifibrotic and Anti-Inflammatory Actions of α-Melanocytic Hormone: New Roles for an Old Player

Cited by 19 publications

References 186 publications

Serum levels of hormones regulating appetite in patients with cystic fibrosis − a single-center, cross-sectional study

Serum levels of hormones regulating appetite in patients with cystic fibrosis − a single-center, cross-sectional study

Focus on the Contribution of Oxidative Stress in Skin Aging

The Dark Side of Melanin Secretion in Cutaneous Melanoma Aggressiveness

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