1,25-(OH)2D3 protects Schwann cells against advanced glycation end products-induced apoptosis through PKA-NF-κB pathway

Xu, Shiqing; Li, Jing; Zhai, Min; Yao, Xiaoqi; Liu, Honglin; Deng, Tingting; Cai, Hao; Zhang, Wan; Zhang, Wenjian; Lou, Jinning; Peng, Liang

doi:10.1016/j.lfs.2019.03.068

Cited by 13 publications

(8 citation statements)

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“…We noticed that the level of vitamin D was lower in the mixed DPN group than in the non-DPN group, which was in line with several previous studies [14][15][16]. Possible mechanisms include vitamin D protecting Schwann cells against advanced glycation end product (AGE)-induced apoptosis [17] and promoting proangiogenic molecules [18]. Further studies are needed to focus on vitamin D in the protection against diabetic neuropathy and the related molecular mechanisms.…”

Section: Clinical Factors Related To Pure Sfn and Mixed Dpnsupporting

confidence: 89%

Better Islet Function and Cardiovascular Autonomic Function in Type 2 Diabetic Patients With Pure Small Fibre Neuropathy Than With Mixed Neuropathy

Wang

et al. 2021

Preprint

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BackgroundThe clinical characteristics and outcomes of small fibre neuropathy (SFN) in Chinese patients with type 2 diabetes have not been thoroughly described, and we investigated metabolic and neurological indexes and the prognosis of type 2 diabetic patients based on skin biopsy. MethodsThirty-four healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intraepidermal nerve fibre density (IENFD). Eighty-nine patients with type 2 diabetes from the Department of Endocrinology at Nanjing Drum Tower Hospital between December 2015 and April 2020 were included in the final study. Metabolic and neurological indexes were evaluated at baseline. Diabetic cardiovascular autonomic function was tested through cardiovascular autonomic reflex tests (CARTs). Seventeen pure SFN subjects and 9 mixed diabetic polyneuropathy (DPN) subjects were reassessed after the follow-up. ResultsLevels of HbA1c and postprandial blood glucose were lower (P=0.005 and P=0.041, respectively), while postprandial C-peptide and insulin were higher (P=0.001 and P=0.019, respectively) in the pure SFN group than in the mixed DPN group. Regarding the CARTs, the mixed DPN group obtained the highest score, indicating the worst cardiovascular autonomic neuropathy (CAN). Among the four CART items, postural BP change was lower while deep breathing max-min was higher in the pure SFN group than in the mixed DPN group (P=0.023 and P=0.040, respectively). A partial correlation showed that there was a negative correlation between IENFD of the distal leg and CART scores (r=-0.513, P=0.001) after adjusting for age and duration of diabetes. Only vitamin B12 (p=0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve (p=0.045) were increased in the 17 patients with pure SFN after the follow-up. However, MCVs of the common peroneal nerve (p=0.025) and tibial nerve (p=0.047) were decreased at the final visit in the mixed DPN group. ConclusionsBetter islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. CART scores were negatively correlated with IENFD in the distal leg even after adjusting for age and duration of diabetes. The metabolic and neurological indexes remained relatively stable in the follow-up of pure SFN subjects.

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Section: Clinical Factors Related To Pure Sfn and Mixed Dpnsupporting

confidence: 89%

Better Islet Function and Cardiovascular Autonomic Function in Type 2 Diabetic Patients With Pure Small Fibre Neuropathy Than With Mixed Neuropathy

Wang

et al. 2021

Preprint

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“…Calcitriol is a potential PARP1 inhibitor in macrophage cell lines, and the association of vitamin D and PARP1 occurs in diabetic cardiomyopathy and nephropathy models (Mabley et al, 2007;Qu et al, 2017;Wang et al, 2020). In a diabetes model simulated by incubating with fetal bovine serum in Schwann cells, calcitriol treatment can reduce cell apoptosis and reduce cleavage of PARP1 (Xu et al, 2019). Vitamin D has not yet been linked to PARP1 or parthanatos in the PD model.…”

Section: Discussionmentioning

confidence: 99%

Calcitriol Alleviates MPP+- and MPTP-Induced Parthanatos Through the VDR/PARP1 Pathway in the Model of Parkinson’s Disease

Wan

et al. 2021

Front. Aging Neurosci.

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The pathogenesis of Parkinson’s disease (PD) is currently unclear. Recent studies have suggested a correlation between vitamin D and PD. Vitamin D and its analogs have protective effects in animal models of PD, but these studies have not clarified the mechanism. Parthanatos is a distinct type of cell death caused by excessive activation of poly (ADP-ribose) polymerase-1 (PARP1), and the activation of PARP1 in PD models suggests that parthanatos may exist in PD pathophysiology. 1,25-Dihydroxyvitamin D3 (calcitriol) is a potential inhibitor of PARP1 in macrophages. This study aimed to investigate whether calcitriol treatment improves PD models and its effects on the parthanatos pathway. A 1-methyl-4-phenylpyridinium (MPP+)-induced cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subacute animal model were selected as the in vitro and in vivo PD models, and calcitriol was applied in these models. Results showed that parthanatos existed in the MPP+-induced cell model and pretreatment with calcitriol improved cell viability, reduced the excessive activation of PARP1, and relieved parthanatos. The application of calcitriol in the MPTP subacute animal model also improved behavioral tests, restored the damage to dopamine neurons, and reduced the activation of PARP1-related signaling pathways. To verify whether calcitriol interacts with PARP1 through its vitamin D receptor (VDR), siRNA, and overexpression plasmids were used to downregulate or overexpress VDR. Following the downregulation of VDR, the expression and activation of PARP1 increased and PARP1 was inhibited when VDR was overexpressed. Coimmunoprecipitation verified the combination of VDR and PARP1. In short, calcitriol can substantially improve parthanatos in the MPP+-induced cell model and MPTP model, and the protective effect might be partly through the VDR/PARP1 pathway, which provides a new possibility for the treatment of PD.

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“…We noted that the level of vitamin D was lower in the mixed DPN group than in the non-DPN group, which is in line with results from several previous studies [ 15 – 17 ]. Possible mechanisms include a role of vitamin D in protecting Schwann cells against advanced glycation end product (AGE)-induced apoptosis [ 18 ] and the promotion of proangiogenic molecules [ 19 ]. Further studies are needed to focus on vitamin D in the protection against diabetic neuropathy and the related molecular mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Better Islet Function and Cardiovascular Autonomic Function in Chinese Type 2 Diabetic Patients with Pure Small Fiber Neuropathy than with Mixed Neuropathy

Wang

et al. 2021

Diabetes Ther

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Introduction The clinical characteristics and outcomes of small fiber neuropathy (SFN) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been thoroughly described. In this study, we investigated the metabolic and neurological indexes and the prognosis of patients with T2DM based on skin biopsy. Methods A total of 34 healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intra-epidermal nerve fiber density (IENFD), and 89 patients with T2DM attending the Nanjing Drum Tower Hospital were evaluated at baseline. Of these 89 patients, 17 with pure SFN and nine with mixed diabetic polyneuropathy (DPN) were reassessed at the end of the follow-up. Results Glycated hemoglobin and postprandial blood glucose levels were lower ( P = 0.005 and P = 0.041, respectively) and postprandial C-peptide and insulin levels were higher ( P = 0.001 and P = 0.019, respectively) in the pure SFN group than in the mixed DPN group. A partial correlation study showed that there was a negative correlation between IENFD of the distal leg and cardiovascular autonomic reflex test (CART) scores ( r = − 0.513, P = 0.001) after adjusting for age and duration of diabetes. Only vitamin B12 level ( P = 0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve ( P = 0.045) were increased in the patients with pure SFN at the final visit while MCVs of the common peroneal nerve ( P = 0.025) and tibial nerve ( P = 0.047) were decreased in the mixed DPN group at the final visit. Conclusion Better islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. The metabolic and neurological indexes remained relatively stable in the patients with pure SFN during the follow-up. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01111-0.

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1,25-(OH)2D3 protects Schwann cells against advanced glycation end products-induced apoptosis through PKA-NF-κB pathway

Cited by 13 publications

References 50 publications

Better Islet Function and Cardiovascular Autonomic Function in Type 2 Diabetic Patients With Pure Small Fibre Neuropathy Than With Mixed Neuropathy

Better Islet Function and Cardiovascular Autonomic Function in Type 2 Diabetic Patients With Pure Small Fibre Neuropathy Than With Mixed Neuropathy

Calcitriol Alleviates MPP+- and MPTP-Induced Parthanatos Through the VDR/PARP1 Pathway in the Model of Parkinson’s Disease

Better Islet Function and Cardiovascular Autonomic Function in Chinese Type 2 Diabetic Patients with Pure Small Fiber Neuropathy than with Mixed Neuropathy

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