The Role of Semaphorins in Metabolic Disorders

Lu, Qiongyu; Zhu, Li

doi:10.3390/ijms21165641

Cited by 29 publications

(18 citation statements)

References 136 publications

(158 reference statements)

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“…These conditions could account for the role of SEMA5A polymorphisms in HRQOL. Additionally, SEMA5A could play a role in chemotherapy-induced peripheral neuropathy (CIPN) given that it is important in the guidance of axons in the central and peripheral nervous system and also that semaphorins are involved in diabetic neuropathy [ 59 , 66 , 67 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach

Adjei

Lopez

Schaid

et al. 2021

Cancers

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Health-related quality of life (HRQOL) is an important prognostic patient-reported outcome in oncology. Because prior studies suggest that HRQOL is, in part, heritable, we performed a GWAS to elucidate genetic factors associated with HRQOL in breast cancer survivors. Physical and mental HRQOL were measured via paper surveys that included the PROMIS-10 physical and mental health domain scales in 1442 breast cancer survivors participating in the Mayo Clinic Breast Disease Registry (MCBDR). In multivariable regression analyses, age and financial concerns were significantly associated with global physical health (age: p = 1.6 × 10−23; financial concerns: p = 4.8 × 10−40) and mental health (age: p = 3.5 × 10−7; financial concerns: p = 2.0 × 10−69). Chemotherapy was associated with worse global mental health (p = 0.01). In the GWAS, none of the SNPs reached the genome-wide association significance threshold of 5 × 10−8 for associations with either global physical or global mental health, however, a cluster of SNPs in SCN10A, particularly rs112718371, appeared to be linked to worse global physical health (p = 5.21 × 10−8). Additionally, SNPs in LMX1B, SGCD, PARP12 and SEMA5A were also moderately associated with worse physical and mental health (p < 10−6). These biologically plausible candidate SNPs warrant further study as possible predictors of HRQOL.

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Section: Discussionmentioning

confidence: 99%

Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach

Adjei

Lopez

Schaid

et al. 2021

Cancers

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“…Accumulating evidence has indicated that semaphorin signaling plays a pivotal role in various pathophysiological processes outside the nervous system [ 2 , 3 ]. Recent studies have focused on the functions of semaphorin signaling in immunometabolic regulation and disorders, such as obesity, diabetes, and atherosclerosis [ 4 – 6 ]. In addition, we recently found that Sema6D signaling induces lipid metabolic reprogramming that is indispensable for anti-inflammatory polarization of macrophages, thus highlighting an essential link between semaphorin signaling and lipid metabolism [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Axon guidance molecules in immunometabolic diseases

2022

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The global prevalence of metabolic diseases, such as obesity, diabetes, and atherosclerosis, is rapidly increasing and has now reached epidemic proportions. Chronic tissue inflammation is a characteristic of these metabolic diseases, indicating that immune responses are closely involved in the pathogenesis of metabolic disorders. However, the regulatory mechanisms underlying immunometabolic crosstalk in these diseases are not completely understood. Recent studies have revealed the multifaceted functions of semaphorins, originally identified as axon guidance molecules, in regulating tissue inflammation and metabolic disorders, thereby highlighting the functional coupling between semaphorin signaling and immunometabolism. In this review, we explore how semaphorin signaling transcends beyond merely guiding axons to controlling immune responses and metabolic diseases.

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“…Plexins are also receptors for semaphorins, a large family of proteins involved in various physiological processes 88 . Semaphorins are involved in a number of diabetic complications including diabetic retinopathy, nephropathy, and neuropathy, osteoporosis, and wound healing 89 . Interestingly, we observed significantly higher levels of CD72 in the SIDD subtype and as CD72 appears to mediate the function of semaphorins in some immune cells 90 , it may provide a potential functional link to PLXNB2.…”

Section: Discussionmentioning

confidence: 99%

Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population

Zaghlool

Halama

Stephan

et al. 2022

Preprint

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Background. Type 2 diabetes (T2D) has a heterogeneous etiology which is increasingly recognized to influence the risk of complications and choice of treatment. A data driven cluster analysis in four separate European populations of patients with type 2 diabetes identified four subtypes of severe insulin dependent (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) (Ahlqvist et al., Lancet Diabetes Endocrinology, 2018). Our aim was to extend this classification to the Arab population of Qatar and characterize the biological processes that differentiate these subtypes in relation to metabolomic and proteomic signatures. Methods. The Ahlqvist et al. subtype clustering approach was applied to 631 individuals with T2D from the Qatar Biobank (QBB) and validated in an independent set of 420 participants from the same population. The association between blood metabolites (n=1,159) and protein levels (n=1,305) with each cluster were established. Findings. The four subtypes of T2D were reproduced and validated in the population of Qatar. Cluster-specific metabolomic and proteomic associations revealed subtype-specific molecular processes. Activation of the complement system with many features of autoimmune diabetes and reduced 1,5-anhydroglucitol (1,5-AG) characterized SIDD, with evidence of impaired insulin signaling in SIRD, elevated leptin and fatty acid binding protein in MOD, whilst MARD appeared to be the healthiest subgroup. Interpretation. We have replicated the four T2D clusters in an Arab population and identified distinct metabolic and proteomic signatures, providing insights into underlying etiology with the potential to deploy subtype-specific treatment options.

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The Role of Semaphorins in Metabolic Disorders

Cited by 29 publications

References 136 publications

Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach

Genetic Variations and Health-Related Quality of Life (HRQOL): A Genome-Wide Study Approach

Axon guidance molecules in immunometabolic diseases

Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population

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