High glucose up-regulates Semaphorin 3A expression via the mTOR signaling pathway in keratinocytes: A potential mechanism and therapeutic target for diabetic small fiber neuropathy

Wu, Liangyan; Li, Mei; Qu, Minli; Li, Xin; Pi, Linhua; Chen, Zi; Zhou, Shanlei; Yi, Xiaoqing; Shi, Xiajie; Wu, Jing; Wang, Shan

doi:10.1016/j.mce.2017.11.025

Cited by 26 publications

(22 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Hyperactive mTORC1 is reported to interfere with synaptic plasticity and to induce chronic neuropathy [ 166 , 167 ]. In line with that, suppression of mTORC1 activity is reported to result in anti-nociceptive effects in experimental models of inflammatory and neuropathic pain [ 166 – 168 ].…”

Section: Type 2 Diabetes – Mtorc1-centric Unifying Paradigmmentioning

confidence: 67%

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

Bar‐Tana

2020

Rev Endocr Metab Disord

View full text Add to dashboard Cite

The current paradigm of type 2 diabetes (T2D) is gluco-centric, being exclusively categorized by glycemic characteristics. The gluco-centric paradigm views hyperglycemia as the primary target, being driven by resistance to insulin combined with progressive beta cells failure, and considers glycemic control its ultimate treatment goal. Most importantly, the gluco-centric paradigm considers the non-glycemic diseases associated with T2D, e.g., obesity, dyslipidemia, hypertension, macrovascular disease, microvascular disease and fatty liver as 'risk factors' and/or 'outcomes' and/or 'comorbidities', rather than primary inherent disease aspects of T2D. That is in spite of their high prevalence (60-90%) and major role in profiling T2D morbidity and mortality. Moreover, the gluco-centric paradigm fails to realize that the non-glycemic diseases of T2D are driven by insulin and, except for glycemic control, response to insulin in T2D is essentially the rule rather than the exception. Failure of the glucocentric paradigm to offer an exhaustive unifying view of the glycemic and non-glycemic diseases of T2D may have contributed to T2D being still an unmet need. An mTORC1-centric paradigm maintains that hyperactive mTORC1 drives the glycemic and non-glycemic disease aspects of T2D. Hyperactive mTORC1 is proposed to act as double-edged agent, namely, to interfere with glycemic control by disrupting the insulin receptor-Akt transduction pathway, while concomitantly driving the non-glycemic diseases of T2D. The mTORC1-centric paradigm may offer a novel perspective for T2D in terms of pathogenesis, clinical focus and treatment strategy.

show abstract

Section: Type 2 Diabetes – Mtorc1-centric Unifying Paradigmmentioning

confidence: 67%

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

Bar‐Tana

2020

Rev Endocr Metab Disord

View full text Add to dashboard Cite

show abstract

“…This is further supported by data showing that total thymus gene expression of SEMA-3A is high in the thymuses from diabetic mice, as is the case of NRP-1 and plexin-1 (data not show). It was previously demonstrated that SEMA-3A was increased in the suprabasal layer of the epidermis with high glucose level conditions, in both diabetic rats and humans, through the mTOR signaling pathway [21]. The mTOR pathway is evolutionarily conserved, and various cell types express mTOR [21].…”

Section: Discussionmentioning

confidence: 99%

“…It was previously demonstrated that SEMA-3A was increased in the suprabasal layer of the epidermis with high glucose level conditions, in both diabetic rats and humans, through the mTOR signaling pathway [21]. The mTOR pathway is evolutionarily conserved, and various cell types express mTOR [21]. Thus, it is not surprising that SEMA-3A is under mTOR signaling regulation in various types of cells [22-24].…”

Section: Discussionmentioning

confidence: 99%

Semaphorin-3A-Related Reduction of Thymocyte Migration in Chemically Induced Diabetic Mice

Francelin

Geniseli

Nagib

et al. 2020

Neuroimmunomodulation

View full text Add to dashboard Cite

Background: Previous work revealed the existence of a severe thymic atrophy with massive loss of immature CD4 + CD8 + thymocytes in animals developing insulin-dependent diabetes, chemically induced by alloxan. Furthermore, the intrathymic expression of chemokines, such as CXCL12, is changed in these animals, suggesting that cell migrationrelated patterns may be altered. One molecular interaction involved in normal thymocyte migration is that mediated by soluble semaphorin-3A and its cognate receptor neuropilin-1. Objectives: We investigated herein the expression and role of semaphorin-3A in the migratory responses of thymocytes from alloxan-induced diabetic mice. We characterized semaphorin-3A and its receptor, neuropilin-1, in thymuses from control and diabetic mice as well as semaphorin-3Adependent migration of developing thymocytes in both

show abstract

“…Nrp1, Nrp2 [108,109] Sema3A Not mentioned [110,111] Sema6A Not mentioned [112] Diabetic wound healing Sema4D PlexinB2 [113] Sema6A Not mentioned [114] Diabetic osteoporosis Sema3A Not mentioned [115][116][117][118]…”

Section: Sema3cmentioning

confidence: 99%

“…Higher Sema3A expression and overactivation of mTOR signaling were accompanied with reduced intraepidermal nerve fiber density (IENFD) in the skin of diabetic patients as compared with control subjects. This pathway could play a critical role in diabetic small fiber neuropathy (SFN) [110].…”

Section: Semaphorins In Diabetic Neuropathymentioning

confidence: 99%

The Role of Semaphorins in Metabolic Disorders

Zhu

2020

IJMS

View full text Add to dashboard Cite

Semaphorins are a family originally identified as axonal guidance molecules. They are also involved in tumor growth, angiogenesis, immune regulation, as well as other biological and pathological processes. Recent studies have shown that semaphorins play a role in metabolic diseases including obesity, adipose inflammation, and diabetic complications, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, diabetic wound healing, and diabetic osteoporosis. Evidence provides mechanistic insights regarding the role of semaphorins in metabolic diseases by regulating adipogenesis, hypothalamic melanocortin circuit, immune responses, and angiogenesis. In this review, we summarize recent progress regarding the role of semaphorins in obesity, adipose inflammation, and diabetic complications.

show abstract

High glucose up-regulates Semaphorin 3A expression via the mTOR signaling pathway in keratinocytes: A potential mechanism and therapeutic target for diabetic small fiber neuropathy

Cited by 26 publications

References 55 publications

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

Semaphorin-3A-Related Reduction of Thymocyte Migration in Chemically Induced Diabetic Mice

The Role of Semaphorins in Metabolic Disorders

Contact Info

Product

Resources

About