Metformin promotes proliferation and suppresses apoptosis in Ox-LDL stimulated macrophages by regulating the miR-34a/Bcl2 axis

Feng, Li; Liu, Tianhua; Yang, Yuya; Xiao, Wenying; Shi, Jun; Xiang, Ming; Tian, Songmei; Liu, Xinbing; Huang, Hongman; Bai, Yanyan

doi:10.1039/c9ra00705a

Cited by 4 publications

(2 citation statements)

References 36 publications

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“…A similar upregulation in miR-34a-5p was recorded in the thoracic aortae of ath diet-fed SD rats. Also, the ox-LDL-treated HUVEC and MDMs showed elevated miR-34a-5p expression, in agreement with the reports of other research groups [42][43][44]. Redox-sensitive NF-kb and P53 are transcription factors of intergenic miR-34a-5p.…”

Section: Corm-a1 Alleviates Mir-34a-5p Expression By Altering Its Tra...supporting

confidence: 91%

CORM-A1 Alleviates Pro-Atherogenic Manifestations via miR-34a-5p Downregulation and an Improved Mitochondrial Function

et al. 2023

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Atherogenesis involves multiple cell types undergoing robust metabolic processes resulting in mitochondrial dysfunction, elevated reactive oxygen species (ROS), and consequent oxidative stress. Carbon monoxide (CO) has been recently explored for its anti-atherogenic potency; however, the effects of CO on ROS generation and mitochondrial dysfunction in atherosclerosis remain unexplored. Herein, we describe the anti-atherogenic efficacy of CORM-A1, a CO donor, in in vitro (ox-LDL-treated HUVEC and MDMs) and in vivo (atherogenic diet-fed SD rats) experimental models. In agreement with previous data, we observed elevated miR-34a-5p levels in all our atherogenic model systems. Administration of CO via CORM-A1 accounted for positive alterations in the expression of miR-34a-5p and transcription factors/inhibitors (P53, NF-κB, ZEB1, SNAI1, and STAT3) and DNA methylation pattern, thereby lowering its countenance in atherogenic milieu. Inhibition of miR-34a-5p expression resulted in restoration of SIRT-1 levels and of mitochondrial biogenesis. CORM-A1 supplementation further accounted for improvement in cellular and mitochondrial antioxidant capacity and subsequent reduction in ROS. Further and most importantly, CORM-A1 restored cellular energetics by improving overall cellular respiration in HUVECs, as evidenced by restored OCR and ECAR rates, whereas a shift from non-mitochondrial to mitochondrial respiration was observed in atherogenic MDMs, evidenced by unaltered glycolytic respiration and maximizing OCR. In agreement with these results, CORM-A1 treatment also accounted for elevated ATP production in both in vivo and in vitro experimental models. Cumulatively, our studies demonstrate for the first time the mechanism of CORM-A1-mediated amelioration of pro-atherogenic manifestations through inhibition of miR-34a-5p expression in the atherogenic milieu and consequential rescue of SIRT1-mediated mitochondrial biogenesis and respiration.

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Section: Corm-a1 Alleviates Mir-34a-5p Expression By Altering Its Tra...supporting

confidence: 91%

CORM-A1 Alleviates Pro-Atherogenic Manifestations via miR-34a-5p Downregulation and an Improved Mitochondrial Function

et al. 2023

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“…Metformin treatment increased the immunostaining of BCl2 and decreased immunostaining of active caspase3 and BAX, these finding suggest that metformin could suppress the uterine apoptosis by upregulating BCl2 proteins. It has been shown that metformin suppresses apoptosis by upregulating BCl2 expression in the macrophage cells (Feng et al, 2019). It has been shown that metformin ameliorates uterine defects in the polycystic ovary syndrome rat model (Y. Zhang et al, 2017); on the other hand, it has also been emphasized that metformin might be important to overcome aging and aging‐related diseases (Soukas et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Effects of metformin on the uterus of d‐galactose‐induced aging mice: Histomorphometric, immunohistochemical localization (B‐cell lymphoma 2, Bcl2‐associated X protein, and active capase3), and oxidative stress study

Rempuia

Anima

Jeremy³

et al. 2022

J Exp Zool Pt A

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D-galactose (DG)-induced rodent aging model has widely been used for the study of age-related dysfunctions of various organs, including gonads and uterus. Antidiabetic drug metformin has gained an attention as antiaging drug in model organism and human but its effect on uterus has not been studied in relation to induced aging. Therefore, we investigated the effect of metformin on uterus of DG-induced aging mice model. Mice were randomly divided into three groups, that is, control (CN), DG-induced aging model and aging model treated with metformin. Histomorphometric results showed significantly decreased number of uterine glands, endometrial thickness, and increased luminal epithelium height in aging model. Furthermore, metformin resumed the number of uterine glands, endometrial thickness, and luminal epithelium height up to CN group. Metformin has also significantly decreased the ageassociated oxidative stress (malondialdehyde and lipid hydroperoxide). Superoxide dismutase was significantly decreased in both treated groups compared to the CN group. However, catalase and glutathione peroxidase enzymes were significantly increased by metformin compared to the aging model. Immunostaining of active caspase3 and BAX were intense in the endometrium of aging model compare to CN-and metformin-treated groups. Localization of B-cell lymphoma 2 (Bcl2) showed intense immunostaining in the uterus of CN-and metformin-treated groups, with mild immunostaining in aging model. Our observations suggested that metformin treatment might be helpful for management of age-associated uterine dysfunctions.Moreover, it may be concluded that metformin might ameliorate uterine dysfunctions by reducing oxidative stress, suppressing apoptosis, and increasing the survival/ antiapoptotic protein Bcl2.

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A parallel and cascade control system: magnetofection of miR125b for synergistic tumor-association macrophage polarization regulation and tumor cell suppression in breast cancer treatment

Chen

et al. 2020

Nanoscale

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Metformin promotes proliferation and suppresses apoptosis in Ox-LDL stimulated macrophages by regulating the miR-34a/Bcl2 axis

Abstract: Metformin, an antidiabetic drug, has been reported to be involved in atherosclerosis (AS).

Cited by 4 publications

References 36 publications

CORM-A1 Alleviates Pro-Atherogenic Manifestations via miR-34a-5p Downregulation and an Improved Mitochondrial Function

CORM-A1 Alleviates Pro-Atherogenic Manifestations via miR-34a-5p Downregulation and an Improved Mitochondrial Function

Effects of metformin on the uterus of d‐galactose‐induced aging mice: Histomorphometric, immunohistochemical localization (B‐cell lymphoma 2, Bcl2‐associated X protein, and active capase3), and oxidative stress study

A parallel and cascade control system: magnetofection of miR125b for synergistic tumor-association macrophage polarization regulation and tumor cell suppression in breast cancer treatment

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