Endogenous sulfur dioxide alleviates collagen remodeling via inhibiting TGF-β/Smad pathway in vascular smooth muscle cells

Huang, Yaqian; Shen, Zhizhou; Chen, Qinghua; Huang, Pan; Zhang, Heng; Du, Shuxu; Geng, Bin; Zhang, Chunyu; Li, Kun; Tang, Chaoshu; Du, Junbao; Jin, Hongfang

doi:10.1038/srep19503

Cited by 32 publications

(17 citation statements)

References 36 publications

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“…To investigate the effects of ET-1 on the endogenous SO 2 pathway and its mechanisms in VSMCs, cells were divided into the following groups: control group, 10 -6 M ET-1 group, N-acetyl-L-cysteine (NAC) group, NAC+10 -6 M ET-1 group, glutathione (GSH) group, and GSH+10 -6 M ET-1 group. [27]. After drug stimulation for 48 h, an SO 2 fluorescent probe working fluid (10 μM) was added to the medium of cells and incubated for 30 min at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Endothelin-1 Downregulates Sulfur Dioxide/Aspartate Aminotransferase Pathway via Reactive Oxygen Species to Promote the Proliferation and Migration of Vascular Smooth Muscle Cells

Tian

Zhang

Huang

et al. 2020

Oxidative Medicine and Cellular Longevity

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The regulatory mechanisms for proliferation and migration of vascular smooth muscle cells have not yet been clear. The present study was designed to investigate whether and how endothelin-1 (ET-1) impacted the generation of endogenous sulfur dioxide (SO2) in rat vascular smooth muscle cell (VSMC) proliferation and migration. Primary VSMCs and purified aspartate aminotransferase (AAT) protein were used in this study. We found that in the presence of ET-1, the expression of PCNA and Ki-67 was upregulated and the migration of VSMCs was promoted, while the AAT activity and SO2 levels in VSMCs were reduced without any changes in AAT1 and AAT2 expression. SO2 supplementation successfully prevented the ET-1-facilitated expression of PCNA and Ki-67 and the migration of VSMCs. Interestingly, ET-1 significantly increased reactive oxygen species (ROS) production in association with SO2/AAT pathway downregulation in VSMCs compared with controls, while the ROS scavenger N-acetyl-L-cysteine (NAC) and the antioxidant glutathione (GSH) significantly abolished the ET-1-stimulated downregulation of the SO2/AAT pathway. Moreover, the AAT activity was reduced in purified protein after the treatment for 2 h. However, NAC and GSH blocked the hydrogen peroxide-induced AAT activity reduction. In conclusion, our results suggest that ET-1 results in the downregulation of the endogenous SO2/AAT pathway via ROS generation to enhance the proliferation and migration of VSMCs.

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Section: Methodsmentioning

confidence: 99%

Endothelin-1 Downregulates Sulfur Dioxide/Aspartate Aminotransferase Pathway via Reactive Oxygen Species to Promote the Proliferation and Migration of Vascular Smooth Muscle Cells

Tian

Zhang

Huang

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Recent studies have found that SO 2 improved the ISO-induced myocardial apoptosis of the rats ( 32 ). Some studies have shown that SO 2 gas performs many biological functions, such as vasodilation, improvement of vascular and collagen remodelling; it also inhibits inflammation and autoxidation and exerts an important protective effect on vascular diseases ( 33 – 36 ), such as pulmonary arterial hypertension, myocardial ischaemia-reperfusion injury, myocardial hypertrophy, spontaneous hypertension and acute lung injury ( 37 – 40 ). However, the role of SO 2 in diabetic myocardial fibrosis and the relevant regulatory mechanism have not been studied yet.…”

Section: Discussionmentioning

confidence: 99%

Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats

Liu¹,

Liu²,

Tan³

et al. 2017

Molecular Medicine Reports

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Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)-generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo-MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L-Aspartic acid β-hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra-peritoneal injection of STZ (40 mg/kg) Following model establishment, intra-peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo-MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis-associated protein B-cell lymphoma associated protein X, caspase-3 and caspase-9 were upregulated, and Bcl-2 expression was downregulated. The expression of ERS and Hippo-MST pathway-associated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these above-mentioned changes were reversed by SO2 treatment. Compared with STZ group, the HDX group had a further increase of myocardial fibrosis and apoptosis, while there were no statistically significant differences in the expression of Bax/Bcl-2, caspase-3, caspase-9 and ERS and Hippo-MST pathway-associated proteins. The results of the present study demonstrated that the gaseous signal molecule SO2 can effectively improve the myocardial fibrosis of diabetic rats, and its mechanism may be associated with reduced apoptosis and ERS by downregulated Hippo-MST pathway.

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“…Skin care is crucial in preventing skin breakdown and venous ulcers especially during kidney dysfunction [ 15 ]. Sometimes permanent deformation also sets in skin when the remodelling capability of collagen [ 16 ] is collapsed, as collagen is the one that binds muscles and bones with skin. The exterior manifestation of muscular changes, hydration [ 17 ] and wrinkles contribute to skin texture when viewed through a digital camera.…”

Section: Gfr Computationmentioning

confidence: 99%

Assessment of chronic kidney disease using skin texture as a key parameter: for South Indian population

Udhayarasu¹,

Ramakrishnan²,

Periasamy

2017

Healthc. technol. lett.

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Periodical monitoring of renal function, specifically for subjects with history of diabetic or hypertension would prevent them from entering into chronic kidney disease (CKD) condition. The recent increase in numbers may be due to food habits or lack of physical exercise, necessitates a rapid kidney function monitoring system. Presently, it is determined by evaluating glomerular filtration rate (GFR) that is mainly dependent on serum creatinine value and demographic parameters and ethnic value. Attempted here is to develop ethnic parameter based on skin texture for every individual. This value when used in GFR computation, the results are much agreeable with GFR obtained through standard modification of diet in renal disease and CKD epidemiology collaboration equations. Once correlation between CKD and skin texture is established, classification tool using artificial neural network is built to categorise CKD level based on demographic values and parameter obtained through skin texture (without using creatinine). This network when tested gives almost at par results with the network that is trained with demographic and creatinine values. The results of this Letter demonstrate the possibility of non-invasively determining kidney function and hence for making a device that would readily assess the kidney function even at home.

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Endogenous sulfur dioxide alleviates collagen remodeling via inhibiting TGF-β/Smad pathway in vascular smooth muscle cells

Cited by 32 publications

References 36 publications

Endothelin-1 Downregulates Sulfur Dioxide/Aspartate Aminotransferase Pathway via Reactive Oxygen Species to Promote the Proliferation and Migration of Vascular Smooth Muscle Cells

Endothelin-1 Downregulates Sulfur Dioxide/Aspartate Aminotransferase Pathway via Reactive Oxygen Species to Promote the Proliferation and Migration of Vascular Smooth Muscle Cells

Gaseous signalling molecule SO2 via Hippo-MST pathway to improve myocardial fibrosis of diabetic rats

Assessment of chronic kidney disease using skin texture as a key parameter: for South Indian population

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