The intact parasympathetic nerve promotes submandibular gland regeneration through ductal cell proliferation

Wang, Xue; Li, Zhilin; Shao, Qi; Zhang, Chunmei; Han, Zhengxue; Wang, Songlin; Qin, Lizheng

doi:10.1111/cpr.13078

Cited by 10 publications

(15 citation statements)

References 36 publications

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“…Given that the origin of the parasympathetic preganglionic is neurons, SSN plays a key role in innervating lacrimal gland and SMG ( Mitoh et al, 2017 ). Previous studies have reported that parasympathetic denervation give rise to loss in SMG weight and decrease in AQP5 expression ( Azlina et al, 2010 ; Wang et al, 2021 ), which was also observed in our study ( Figures 4B,F ). Therefore, we speculated that hyperglycemia may not only cause SMG injury, but also induce SSN damage, both of which lead to diabetes xerostomia.…”

Section: Discussionsupporting

confidence: 91%

“…It has been reported that the expression level of AQP5 in SMG is regulated by the parasympathetic nerve ( Hosoi et al, 2020 ). Parasympathetic nerves are closely associated with SGs regeneration, and intact parasympathetic innervation facilitates SMGs regeneration ( Wang et al, 2021 ). Given that the origin of the parasympathetic preganglionic is neurons, SSN plays a key role in innervating lacrimal gland and SMG ( Mitoh et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

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Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway

Zhang

Nong

et al. 2021

Front. Pharmacol.

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Polydipsia and xerostomia are the most common complications that seriously affect oral health in patients with diabetes. However, to date, there is no effective treatment for diabetic xerostomia. Recent studies have reported that artesunate (ART) and metformin (Met) improve salivary gland (SG) hypofunction in murine Sjögren’s syndrome. Therefore, aim of this study was to investigate the effect and underlying mechanism of artesunate (ART) alone and in combination with metformin (Met) on hyposalivation in type 2 diabetes mellitus (T2DM) rats. T2DM rats were induced using a high-fat diet and streptozotocin. SPF male Sprague–Dawley rats were divided into the following five groups: normal control group, untreated diabetic group, ART-treated diabetic group (50 mg/kg), Met-treated diabetic group (150 mg/kg), and ART/Met co-treated diabetic group (50 mg/kg ART and 150 mg/kg Met). ART and Met were intragastrically administered daily for 4 weeks. The general conditions, diabetes parameters and serum lipids were evaluated after drug treatment. Furthermore, we observed changes in the central superior salivatory nucleus (SSN) and SG, and changes in the AQP5 expression, parasympathetic innervation (AChE and BDNF expression), and PI3K/AKT pathway- (p-AKT, and p-PI3K), apoptosis- (Bax, Bcl-2, and Caspase3), and autophagy- (LC3 and P62) related markers expression in T2DM rats after treatment. Our results showed that ART or Met alone and ART/Met combination attenuated a range of diabetic symptoms, including weight loss, urine volume increase, water consumption increase, hyperglycemia, insulin resistance, glucose intolerance and dyslipidemia. More importantly, we found that these three treatments, especially ART/Met combination, mitigated hyposalivation in the T2DM rats via improving the central SSN and SGs damage in hyperglycemia. Our data also indicated that ART/Met attenuated SG damage though regulating the PI3K/Akt pathway to inhibit apoptosis and autophagy of SGs in the T2DM rats. Moreover, ART/Met preserved parasympathetic innervation (AChE and BDNF expression) in SGs to alleviate diabetes-induced hyposalivation likely through rescuing central SSN damage. Taken together, these findings might provide a novel rationale and treatment strategy for future treatment of diabetes-induced xerostomia in the clinic.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway

Zhang

Nong

et al. 2021

Front. Pharmacol.

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“…The immunohistochemical assay was performed as previously described [ 27 ]. The primary antibodies against VEGFA, CD31, and PCNA were used.…”

Section: Methodsmentioning

confidence: 99%

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Ischemia-Reperfusion Injury and Promote Survival of Skin Flaps in Rats

Niu

Yang

et al. 2022

Life

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Free tissue flap transplantation is a classic and important method for the clinical repair of tissue defects. However, ischemia-reperfusion (IR) injury can affect the success rate of skin flap transplantation. We used a free abdomen flap rat model to explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-exosomes) against the IR injury of the skin flap. Exosomes were injected through the tail vein and the flaps were observed and obtained on day 7. We observed that BMSCs-exosomes significantly reduced the necrotic lesions of the skin flap. Furthermore, BMSCs-exosomes relieved oxidative stress and reduced the levels of inflammatory factors. Apoptosis was evaluated via the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and Western blot analysis of Bax, Bcl-2. Simultaneously, BMSCs-exosomes promoted the formation of new blood vessels in the IR flap, as confirmed by the increased expression level of VEGFA and the fluorescence co-staining of CD31 and PCNA. Additionally, BMSCs-exosomes considerably increased proliferation and migration of human umbilical vein endothelial cells and promoted angiogenesis in vitro. BMSCs-exosomes could be a promising cell-free therapeutic candidate to reduce IR injury and promote the survival of skin flaps.

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“…Under anesthesia, the unilateral parotid excretory duct was ligated, according to a previously reported procedure [18]. Salivary glands recover when the ligation is released 7 days after the duct ligation [19,20]. We previously reported that parotid gland morphology showed weak atrophy of acinar cells in some samples on day 3 of duct ligation, whereas most acinar cells in the parotid gland were atrophied on day 7 of duct ligation [18].…”

Section: Ductmentioning

confidence: 99%

Acinar Cell Proliferation Promoted by BMP2 in Injured Mouse Parotid Gland: BMP2 Promotes Cell Proliferation in Parotid Gland

Yokoyama

Katsumata-Kato

Fujita-Yoshigaki

2023

International Journal of Dentistry

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Objective. To identify factors that affect salivary gland recovery, we investigated the expression and function of bone morphogenetic protein 2 (BMP2) in mice. Materials and Methods. Using a micro clip, mice parotid glands were removed 7 days after the ligation of the unilateral parotid excretory duct. Thereafter, they were weighed and stained with hematoxylin and eosin, and BMP2 expression was examined via real-time reverse transcription-polymerase chain reaction. Primary cultures of parotid glands were prepared, and BMP2 protein was added to the culture medium for 48 hr to examine its effect on cell proliferation. E-cadherin and vimentin expression was examined using western blotting. Finally, immunohistochemical staining using an anti-Ki67 antibody was performed. Results. Duct-ligated parotid glands weighed less than those that were collected after sham surgery and showed acinar cell atrophy. They also showed higher BMP2 expression than control glands. Primary-cultured parotid acinar cells supplemented with BMP2 showed higher proliferative potential than control cells. Furthermore, they showed E-cadherin, but not vimentin, expression, and their percentage of Ki67-positive cells were higher than that corresponding to the controls. Conclusions. Injury to salivary glands by excretory duct ligation increased BMP2 expression, which may be involved in maintaining salivary gland function by inducing acinar cell proliferation.

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The intact parasympathetic nerve promotes submandibular gland regeneration through ductal cell proliferation

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 10 publications

References 36 publications

Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway

Artesunate Combined With Metformin Ameliorate on Diabetes-Induced Xerostomia by Mitigating Superior Salivatory Nucleus and Salivary Glands Injury in Type 2 Diabetic Rats via the PI3K/AKT Pathway

Exosomes Derived from Bone Marrow Mesenchymal Stem Cells Alleviate Ischemia-Reperfusion Injury and Promote Survival of Skin Flaps in Rats

Acinar Cell Proliferation Promoted by BMP2 in Injured Mouse Parotid Gland: BMP2 Promotes Cell Proliferation in Parotid Gland

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