Project description:Chronic kidney disease (CKD) is one of the major global health problems with high incidence, poor prognosis and high medical cost. However, few pharmacological options are available for CKD. Metformin is widely used for treatment of type-2 diabetes, but recent works showed that metformin ameliorates tumor progression, inflammatory disease and tissue fibrosis. Whether metformin ameliorates non-diabetic chronic glomerular disease and CKD is unexplored. Here we showed that metformin or losartan (used as control) has protective effects against CKD by suppressing proteinuria, renal inflammation, fibrosis and glomerular injury in Alport syndrome mouse model, which spontaneously manifests chronic glomerular and kidney disease. Transcriptome analysis showed that metformin and losartan influenced molecular pathways of metabolism and inflammation, respectively. While metformin specifically affected genes that were classified as metabolic regulators, losartan specifically altered genes that were classified as inflammatory regulators. Metformin also induced multiple signaling pathways not affected by losartan. Overall, metformin ameliorates non-diabetic chronic glomerular diseases, and could be considered a therapeutic option for CKD. We used microarrays to investigate the global gene expression underlying the protective effects of metformin on Alport syndrome mice model
Project description:We have evaluated the microRNA expression profile of SUM159 cells stably infected with a control shRNA or a dicer-targeting shRNA treated with vehicle or metformin for 24 hrs at non cytotoxic doses. microRNA expression was evaluated from total RNA extracted from logaritmically growing SUM159 cells stably expressing a control shRNA or a dicer-targeting shRNA and treated with vehicle (PBS) or metformin (0.5mM) for 24 hrs.
Project description:This experiment aimed to discover the effects of metformin on mouse liver and kidney tissue. The effects were seen by comparing the liver of the metformin group to the liver of a control group of mice treated given saline solution.
Project description:We have evaluated the microRNA expression profile of SUM159 cells stably infected with a control shRNA or a dicer-targeting shRNA treated with vehicle or metformin for 24 hrs at non cytotoxic doses.
Project description:COVID-19 associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. It is unclear how susceptible human kidneys are to direct SARS-CoV-2 infection and whether pharmacologic manipulation of the renin-angiotensin II signaling (RAS) pathway modulates this susceptibility. Using induced pluripotent stem cell derived kidney organoids, SARS-CoV-1, SARS-CoV-2 and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2, NRP1 or DPP4) and protease (TMPRSS2, TMPRSS4, FURIN, CTSB or CTSL), was identified primarily amongst proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in COVID-19 patients, inhibited angiotensin II mediated internalization of ACE2, upregulated interferon stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.
Project description:Background: Metformin, one of the first-line medication for the treatment of type 2 diabetes and gestational diabetes, has recently be suggested for targeting cardiovascular disease, cancer and aging. Therefore, current understanding of the mechanism of this drug is incompletely understood, and the function of multiple tissues, other than liver metabolism alone, may be influenced. Methods: The wildtype healthy mice treated with metformin were compared with controls (treated with double distilled water). The transcriptome changes with/without metformin treatment were probed by using high-throughput RNA-seq techniques Results: A comprehensive mouse transcriptome map with metformin treatment across ten tissues including aorta, eyeball, brain, adipose tissue, heart, kidney, liver, skeletal muscle, stomach and testis, was provided. Function enrichment, network characteristics and disease association of the differentially expressed genes were analyzed. We also compared our expression profiles with related microarray data in order to find conditions that share similar expression profiles with metformin treatment. Conclusions: This dataset could serve as a baseline resource for investigating the potential beneficial or adverse effects of metformin across different tissues.
Project description:This experiment includes treatment of human pulmonary fibroblasts obtained from IPF patients with metformin. Since, we would like to investigate the transcriptome profile of these samples following metformin treatment. There will be two groups consist of four samples each. First group treated with metformin for 72 hours, while the second group treated with vehicle.
Project description:The role of the renin-angiotensin system in chronic kidney disease involves multiple peptides and receptors. Exerting antipodal pathophysiological mechanisms, renin inhibition and AT1 antagonism ameliorate renal damage. This is a comparison between the renin inhibitor aliskiren with the At1 antagonist losartan in mice with chronic kidney disease due to renal ablation. Renal tissue from ablated mice was used after 6-week treatment with either 500 mg/l losartan or 50 mg/kg aliskiren per day (n = 5)
Project description:NOD-SCID mouse were treated with metformin for 11 and 24 days, the gene expression of tumors of mice treated with metformin were compared with respect to the expression of the tumors of mouse treated with vehicle (water). We evaluated the effect of Metformin (525mg/kg/day) for two times of treatment (11 days and 24 days) upon gene expression in tumors of mice treated or not with metformin. Metformin treatment decreased of tumor growth in both treatment regimens. A complete genomic analysis of transcriptomic status after treatment with metformin revealed an impact on the overall expression of transcripts.