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Ageing Research Reviews Nov 2023Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its... (Review)
Review
Elabela (ELA), Apela or Toddler peptide is a hormone peptide belonging to the adipokine group and a component of apelinergic system, discovered in 2013-2014. Given its high homology with apelin, the first ligand of APJ receptor, ELA likely mediates similar effects. Increasing evidence shows that ELA has a critical function not only in embryonic development, but also in adulthood, contributing to physiological and pathological conditions, such as the onset of age-related diseases (ARD). However, still little is known about the mechanisms and molecular pathways of ELA, as well as its precise functions in ARD pathophysiology. Here, we report the mechanisms by which ELA/APJ signaling acts in a very complex network of pathways for the maintenance of physiological functions of human tissue and organs, as well as in the onset of some ARD, where it appears to play a central role. Therefore, we describe the possibility to use the ELA/APJ pathway, as novel biomarker (predictive and diagnostic) and target for personalized treatments of ARD. Its potentiality as an optimal peptide candidate for therapeutic ARD treatments is largely described, also detailing potential current limitations.
Topics: Pregnancy; Female; Humans; Peptide Hormones; Apelin Receptors; Signal Transduction; Aging
PubMed: 37776977
DOI: 10.1016/j.arr.2023.102076 -
Theranostics 2023Ischemia-reperfusion injury (I/R) is a common cause of acute kidney injury (AKI). Post-ischemic recovery of renal blood supply plays an important role in attenuating...
Ischemia-reperfusion injury (I/R) is a common cause of acute kidney injury (AKI). Post-ischemic recovery of renal blood supply plays an important role in attenuating injury. Exogenous application of elabela (ELA) peptides has been demonstrated by us and others to alleviate AKI, partly through its receptor APJ. However, the endogenous role of ELA in renal I/R remains unclear. Renal tubule specific ELA knockout ( KO) mice challenged with bilateral or unilateral I/R were used to investigate the role of endogenous ELA in renal I/R. RNA-sequencing analysis was performed to unbiasedly investigate altered genes in kidneys of KO mice. Injured mice were treated with ELA32 peptide, Nω-hydroxy-nor-L-arginine (nor-NOHA), prostaglandin E2 (PGE2), Paricalcitol, ML221 or respective vehicles, individually or in combination. ELA is mostly expressed in renal tubules. Aggravated pathological injury and further reduction of renal microvascular blood flow were observed in KO mice during AKI and the following transition to chronic kidney disease (AKI-CKD). RNA-seq analysis suggested that two blood flow regulators, arginine metabolizing enzyme arginase 2 (ARG2) and PGE2 metabolizing enzyme carbonyl reductases 1 and 3 (CBR1/3), were altered in injured KO mice. Notably, combination application of an ARG2 inhibitor nor-NOHA, and Paricalcitol, a clinically used activator for PGE2 synthesis, alleviated injury-induced AKI/AKI-CKD stages and eliminated the worst outcomes observed in KO mice. Moreover, while the APJ inhibitor ML221 blocked the beneficial effects of ELA32 peptide on AKI, it showed no effect on combination treatment of nor-NOHA and Paricalcitol. An endogenous tubular ELA-APJ axis regulates renal microvascular blood flow that plays a pivotal role in I/R-induced AKI. Furthermore, improving renal blood flow by inhibiting ARG2 and activating PGE2 is an effective treatment for AKI and prevents the subsequent AKI-CKD transition.
Topics: Mice; Animals; Microcirculation; Dinoprostone; Kidney; Acute Kidney Injury; Renal Insufficiency, Chronic; Reperfusion Injury; Ischemia; Peptide Hormones; Reperfusion
PubMed: 37351176
DOI: 10.7150/thno.84308 -
Handbook of Experimental Pharmacology 2022The enteroendocrine system coordinates the physiological response to food intake by regulating rates of digestion, nutrient absorption, insulin secretion, satiation and...
The enteroendocrine system coordinates the physiological response to food intake by regulating rates of digestion, nutrient absorption, insulin secretion, satiation and satiety. Gut hormones with important anorexigenic and/or insulinotropic roles include glucagon-like peptide 1 (GLP-1), peptide YY (PYY), cholecystokinin (CCK) and glucose-dependent insulinotropic peptide (GIP). High BMI or obesogenic diets do not markedly disrupt this enteroendocrine system, which represents a critical target for inducing weight loss and treating co-morbidities in individuals with obesity.
Topics: Cholecystokinin; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Obesity; Peptide YY
PubMed: 35419621
DOI: 10.1007/164_2022_582 -
Frontiers in Endocrinology 2024Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which... (Review)
Review
Anti-Müllerian hormone (AMH) is a Sertoli cell-secreted glycoprotein involved in male fetal sex differentiation: it provokes the regression of Müllerian ducts, which otherwise give rise to the Fallopian tubes, the uterus and the upper part of the vagina. In the first trimester of fetal life, AMH is expressed independently of gonadotropins, whereas from the second trimester onwards AMH testicular production is stimulated by FSH and oestrogens; at puberty, AMH expression is inhibited by androgens. AMH has also been suggested to participate in testicular descent during fetal life, but its role remains unclear. Serum AMH is a well-recognized biomarker of testicular function from birth to the first stages of puberty. Especially in boys with nonpalpable gonads, serum AMH is the most useful marker of the existence of testicular tissue. In boys with cryptorchidism, serum AMH levels reflect the mass of functional Sertoli cells: they are lower in patients with bilateral than in those with unilateral cryptorchidism. Interestingly, serum AMH increases after testis relocation to the scrotum, suggesting that the ectopic position result in testicular dysfunction, which may be at least partially reversible. In boys with cryptorchidism associated with micropenis, low AMH and FSH are indicative of central hypogonadism, and serum AMH is a good marker of effective FSH treatment. In patients with cryptorchidism in the context of disorders of sex development, low serum AMH is suggestive of gonadal dysgenesis, whereas normal or high AMH is found in patients with isolated androgen synthesis defects or with androgen insensitivity. In syndromic disorders, assessment of serum AMH has shown that Sertoli cell function is preserved in boys with Klinefelter syndrome until mid-puberty, while it is affected in patients with Noonan, Prader-Willi or Down syndromes.
Topics: Female; Humans; Male; Anti-Mullerian Hormone; Cryptorchidism; Androgens; Follicle Stimulating Hormone; Peptide Hormones
PubMed: 38501100
DOI: 10.3389/fendo.2024.1361032 -
Progress in Lipid Research Jul 2023Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone.... (Review)
Review
Adipokines play a significant role in cardiometabolic diseases. Asprosin, a newly discovered adipokine, was first identified as a glucose-raising protein hormone. Asprosin also stimulates appetite and regulates glucose and lipid metabolism. Its identified receptors so far include Olfr734 and Ptprd. Clinical studies have found that asprosin may be associated with cardiometabolic diseases. Asprosin may have diagnostic and therapeutic potential in obesity, diabetes, metabolic syndrome and atherosclerotic cardiovascular diseases. Herein, the structure, receptors, and functions of asprosin and its relationship with cardiometabolic diseases are summarized based on recent findings.
Topics: Humans; Adipokines; Cardiovascular Diseases; Peptide Hormones; Microfilament Proteins; Peptide Fragments; Fibrillin-1; Glucose
PubMed: 37473965
DOI: 10.1016/j.plipres.2023.101240 -
Peptides Sep 2023
Topics: Peptide Hormones; Cardiovascular System; Heart
PubMed: 37422013
DOI: 10.1016/j.peptides.2023.171062 -
Scientific Data Apr 2022Peptide hormones (also known as hormone peptides and polypeptide hormones) are hormones composed of peptides and are signal transduction molecules produced by a class of...
Peptide hormones (also known as hormone peptides and polypeptide hormones) are hormones composed of peptides and are signal transduction molecules produced by a class of multicellular organisms. It plays an important role in the physiological and behavioral regulation of animals and humans as well as in the growth of plants. In order to promote the research on peptide hormones, we constructed HORDB database. The database currently has a total of 6024 entries, including 5729 peptide hormones, 40 peptide drugs and 255 marketed pharmaceutical preparations information. Each entry provided comprehensive information related to the peptide, including general information, sequence, activity, structure, physical information and literature information. We also added information on IC, EC, ED, target, and whether or not the blood-brain barrier was crossed to the activity information note. In addition, HORDB integrates search and sequence analysis to facilitate user browsing and data analysis. We believe that the peptide hormones information collected by HORDB will promote the design and discovery of peptide hormones, All data are hosted and available in figshare https://doi.org/10.6084/m9.figshare.c.5522241 .
Topics: Animals; Databases, Factual; Humans; Peptide Hormones; Plants; Signal Transduction
PubMed: 35469024
DOI: 10.1038/s41597-022-01287-5 -
Journal of the College of Physicians... Oct 2022To investigate the serum versus insulin-like peptide-6 (INSL-6) levels in men with non-obstructive azoospermia (NOA) and normospermia.
OBJECTIVE
To investigate the serum versus insulin-like peptide-6 (INSL-6) levels in men with non-obstructive azoospermia (NOA) and normospermia.
STUDY DESIGN
Descriptive study.
PLACE AND DURATION OF STUDY
Department of Urology, Balikligol State Hospital and Harran University, Sanliurfa, Turkey, between July and October 2020.
METHODOLOGY
The serum and seminal levels of INSL-6 were measured in men with NOA, and normospermia using a commercially available enzyme-linked immunosorbent assay. Age, body mass index (BMI), hormone profile, testicular volumes and seminal and serum INSL-6 levels were compared between the study groups.
RESULTS
In total, 80 men were included in the study, 40 of whom have NOA and 40 have normospermia. No significant difference was found in the mean age and BMI between the groups (p >0.05). Seminal INSL-6 levels were higher in the normospermia group, although serum and seminal INSL-6 levels were not significantly different in this group (p >0.05). No significant correlation was observed between serum INSL-6 levels and age, BMI,testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and varicocele presence (p >0.05). No significant association was found between seminal INSL-6 levels and age, BMI, FSH, LH, and testosterone levels (p >0.05). However, a significant negative association observed between seminal INSL-6 levels and testicular volume (p <0.05).
CONCLUSION
The seminal INSL-6 levels were approximately 5.5 times higher than the serum INSL-6 levels and survival level of INSL-6 were higher in the normospermia. This suggests that INSL-6 plays an active role in the male reproductive system. However, the mechanism and extent of this effect remain to be elucidated.
KEY WORDS
Infertility, Non-obstructive azoospermia, Insulin-like peptide-6.
Topics: Azoospermia; Follicle Stimulating Hormone; Humans; Insulins; Luteinizing Hormone; Male; Testis; Testosterone
PubMed: 36205264
DOI: 10.29271/jcpsp.2022.10.1238 -
Biomedicine & Pharmacotherapy =... Oct 2023Apelin and Elabela (Ela) are peptides encoded by APLN and APELA, respectively, which act on their receptor APJ and play crucial roles in the body. Recent research has... (Review)
Review
Apelin and Elabela (Ela) are peptides encoded by APLN and APELA, respectively, which act on their receptor APJ and play crucial roles in the body. Recent research has shown that they not only have important effects on the endocrine system, but also promote vascular development and maintain the homeostasis of myocardial cells. From a molecular biology perspective, we explored the roles of Ela and apelin in the cardiovascular system and summarized the mechanisms of apelin-APJ signaling in the progression of myocardial infarction, ischemia-reperfusion injury, atherosclerosis, pulmonary arterial hypertension, preeclampsia, and congenital heart disease. Evidences indicated that apelin and Ela play important roles in cardiovascular diseases, and there are many studies focused on developing apelin, Ela, and their analogues for clinical treatments. However, the literature on the therapeutic potential of apelin, Ela and their analogues and other APJ agonists in the cardiovascular system is still limited. This review summarized the regulatory pathways of apelin/ELA-APJ axis in cardiovascular function and cardiovascular-related diseases, and the therapeutic effects of their analogues in cardiovascular diseases were also included.
Topics: Female; Humans; Pregnancy; Apelin; Apelin Receptors; Cardiovascular Diseases; Cardiovascular System; Peptide Hormones; Signal Transduction
PubMed: 37562237
DOI: 10.1016/j.biopha.2023.115268 -
Nutrients Dec 2022The seminal discoveries that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are major endocrine regulators of vitamin D metabolism led to a... (Review)
Review
The seminal discoveries that parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are major endocrine regulators of vitamin D metabolism led to a significant improvement in our understanding of the pivotal roles of peptide hormones and small proteohormones in the crosstalk between different organs, regulating vitamin D metabolism. The interaction of vitamin D, FGF23 and PTH in the kidney is essential for maintaining mineral homeostasis. The proteohormone FGF23 is mainly secreted from osteoblasts and osteoclasts in the bone. FGF23 acts on proximal renal tubules to decrease production of the active form of vitamin D (1,25(OH)D) by downregulating transcription of 1α-hydroxylase (), and by activating transcription of the key enzyme responsible for vitamin D degradation, 24-hydroxylase (). Conversely, the peptide hormone PTH stimulates 1,25(OH)D renal production by upregulating the expression of 1α-hydroxylase and downregulating that of 24-hydroxylase. The circulating concentration of 1,25(OH)D is a positive regulator of FGF23 secretion in the bone, and a negative regulator of PTH secretion from the parathyroid gland, forming feedback loops between kidney and bone, and between kidney and parathyroid gland, respectively. In recent years, it has become clear that vitamin D signaling has important functions beyond mineral metabolism. Observation of seasonal variations in blood pressure and the subsequent identification of vitamin D receptor (VDR) and 1α-hydroxylase in non-renal tissues such as cardiomyocytes, endothelial and smooth muscle cells, suggested that vitamin D may play a role in maintaining cardiovascular health. Indeed, observational studies in humans have found an association between vitamin D deficiency and hypertension, left ventricular hypertrophy and heart failure, and experimental studies provided strong evidence for a role of vitamin D signaling in the regulation of cardiovascular function. One of the proposed mechanisms of action of vitamin D is that it functions as a negative regulator of the renin-angiotensin-aldosterone system (RAAS). This finding established a novel link between vitamin D and RAAS that was unexplored until then. During recent years, major progress has been made towards a more complete understanding of the mechanisms by which FGF23, PTH, and RAAS regulate vitamin D metabolism, especially at the genomic level. However, there are still major gaps in our knowledge that need to be filled by future research. The purpose of this review is to highlight our current understanding of the molecular mechanisms underlying the interaction between vitamin D, FGF23, PTH, and RAAS, and to discuss the role of these mechanisms in physiology and pathophysiology.
Topics: Humans; Fibroblast Growth Factors; Parathyroid Hormone; Peptide Hormones; Renin-Angiotensin System; Vitamin D; Vitamin D3 24-Hydroxylase; Vitamins
PubMed: 36501215
DOI: 10.3390/nu14235186