6 results on '"Liming Pei"'
Search Results
2. Cardiac Endocrinology
- Author
-
Liming Pei and Juanjuan Zhao
- Subjects
0301 basic medicine ,Cardiac function curve ,medicine.medical_specialty ,business.industry ,Mechanism (biology) ,Disease ,030204 cardiovascular system & hematology ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Circulatory system ,Endocrine system ,Medicine ,Cardiology and Cardiovascular Medicine ,business ,Target organ ,Whole Organism ,Hormone - Abstract
The heart plays a central role in the circulatory system and provides essential oxygen, nutrients, and growth factors to the whole organism. The heart can synthesize and secrete endocrine signals to communicate with distant target organs. Studies of long-known and recently discovered heart-derived hormones highlight a shared theme and reveal a unified mechanism of heart-derived hormones in coordinating cardiac function and target organ biology. This paper reviews the biochemistry, signaling, function, regulation, and clinical significance of representative heart-derived hormones, with a focus on the cardiovascular system. This review also discusses important and exciting questions that will advance the field of cardiac endocrinology.
- Published
- 2020
3. Loss of Mitochondrial Transcription Factor A (TFAM) in Tubule Cells Causes Renal Failure Via Activating the cGAS-STING Innate Immune Pathway
- Author
-
Xin Sheng, Poonam Dhillon, Matthew Palmer, Ki Wung Chung, Joseph A. Baur, Shizheng Huang, Liming Pei, Brett A. Kaufman, Rojesh Shrestha, Chengxiang Qiu, Jihwan Park, and Katalin Susztak
- Subjects
Immune system ,Innate immune system ,Fibrosis ,Stimulator of interferon genes ,Cytosolic DNA-Sensing Pathway ,Renal fibrosis ,medicine ,TFAM ,Biology ,medicine.disease ,Cell biology ,Proinflammatory cytokine - Abstract
Kidney fibrosis is characterized by tubule atrophy, compromised bioenergetics and proinflammatory gene expression. The relationship between these events are poorly understood. In patient samples, the expression of TFAM and mitochondrial genes correlates with kidney fibrosis. Mice with tubule specific deletion of TFAM (Ksp-Cre/Tfam flox/flox) developed severe mitochondrial loss and decline of ATP content by 6 weeks of age. Progressive azotemia, kidney fibrosis and death of the animals was only observed after 12 weeks of age. Mechanistic studies demonstrated that aberrant mtDNA packaging upon TFAM deficiency in tubule cells resulted in escape of mtDNA into the cytosol, activation of the cytosolic DNA sensing pathway, the Stimulator of interferon genes (STING), resulting in cytokine expression and immune cell recruitment. Genetic deletion or pharmacological inhibition of STING ameliorated TFAM-loss induced kidney fibrosis, demonstrating, that in addition to its essential role in metabolism, TFAM sequesters mtDNA to prevent the activation of innate immune pathways and fibrosis.
- Published
- 2019
4. The Nuclear Receptor ESRRA Protects from Kidney Disease by Coupling Metabolism and Differentiation
- Author
-
Seung Yub Han, Jihwan Park, Poonam Dhillon, Patrícia Rezende do Prado, Michael S. Balzer, Liming Pei, Shizheng Huang, Hyun Mi Kang, Shatakshee Chatterjee, Rojesh Shrestra, Juanjuan Zhao, Pieterjan Dierickx, Katalin Susztak, Kirill Batmanov, Mingyao Li, Hongbo Liu, Junhyong Kim, Xin Sheng, Nuria Montserrat, Felipe Prosper, Lingzhi Li, Juan P. Romero, Carmen Hurtado del Pozo, and Tomohito Doke
- Subjects
Male ,0301 basic medicine ,Cell type ,Physiology ,Cellular differentiation ,Biology ,Article ,Transcriptome ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Gene expression ,medicine ,Animals ,Receptor ,Molecular Biology ,Cells, Cultured ,Mice, Knockout ,Kidney ,Kidney diseases ,Cell Differentiation ,Cell Biology ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Receptors, Estrogen ,Nuclear receptor ,Malalties del ronyó ,RNA ,Kidney Diseases ,030217 neurology & neurosurgery ,Kidney disease - Abstract
Kidney disease is poorly understood because of the organ’s cellular diversity. We used single-cell RNA sequencing not only in resolving differences in injured kidney tissue cellular composition but also in cell-type-specific gene expression in mouse models of kidney disease. This analysis highlighted major changes in cellular diversity in kidney disease, which markedly impacted whole-kidney transcriptomics outputs. Cell-type-specific differential expression analysis identified proximal tubule (PT) cells as the key vulnerable cell type. Through unbiased cell trajectory analyses, we show that PT cell differentiation is altered in kidney disease. Metabolism (fatty acid oxidation and oxidative phosphorylation) in PT cells showed the strongest and most reproducible association with PT cell differentiation and disease. Coupling of cell differentiation and the metabolism was established by nuclear receptors (estrogen-related receptor alpha [ESRRA] and peroxisomal proliferation-activated receptor alpha [PPARA]) that directly control metabolic and PT-cell-specific gene expression in mice and patient samples while protecting from kidney disease in the mouse model.
- Published
- 2021
5. Bone marrow NR4A expression is not a dominant factor in the development of atherosclerosis or macrophage polarization in mice
- Author
-
Orla M. Conneely, Rajendra K. Tangirala, Liming Pei, Ajay Chawla, Ayaka Ito, Ronald M. Evans, Lily C. Chao, Peter Tontonoz, Erin Soto, and Cynthia Hong
- Subjects
Male ,Nerve growth factor IB ,Macrophage polarization ,Inflammation ,QD415-436 ,030204 cardiovascular system & hematology ,Biology ,Real-Time Polymerase Chain Reaction ,Biochemistry ,Mice ,03 medical and health sciences ,Nur77 ,0302 clinical medicine ,Endocrinology ,Genetic model ,Nuclear Receptor Subfamily 4, Group A, Member 1 ,medicine ,Animals ,nuclear receptor ,Liver X receptor ,Research Articles ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Macrophages ,Monocyte ,Cell Biology ,Atherosclerosis ,Flow Cytometry ,medicine.anatomical_structure ,Nuclear receptor ,Ly6C ,LDL receptor ,Immunology ,Cancer research ,medicine.symptom - Abstract
The formation of the atherosclerotic lesion is a complex process influenced by an array of inflammatory and lipid metabolism pathways. We previously demonstrated that NR4A nuclear receptors are highly induced in macrophages in response to inflammatory stimuli and modulate the expression of genes linked to inflammation in vitro. Here we used mouse genetic models to assess the impact of NR4A expression on atherosclerosis development and macrophage polarization. Transplantation of wild-type, Nur77⁻/⁻, or Nor1⁻/⁻ null hematopoetic precursors into LDL receptor (LDLR)⁻/⁻ recipient mice led to comparable development of atherosclerotic lesions after high-cholesterol diet. We also observed comparable induction of genes linked to M1 and M2 responses in wild-type and Nur77-null macrophages in response to lipopolysaccharides and interleukin (IL)-4, respectively. In contrast, activation of the nuclear receptor liver X receptor (LXR) strongly suppressed M1 responses, and ablation of signal transductor and activator of transcription 6 (STAT6) strongly suppressed M2 responses. Recent studies have suggested that alterations in levels of Ly6C(lo) monocytes may be a contributor to inflammation and atherosclerosis. In our study, loss of Nur77, but not Nor1, was associated with decreased abundance of Ly6C(lo) monocytes, but this change was not correlated with atherosclerotic lesion development. Collectively, our results suggest that alterations in the Ly6C(lo) monocyte population and bone marrow NR4A expression do not play dominant roles in macrophage polarization or the development of atherosclerosis in mice.
- Published
- 2013
6. The Small Molecule Harmine Is an Antidiabetic Cell-Type-Specific Regulator of PPARγ Expression
- Author
-
Robert Damoiseaux, Enrique Saez, Liming Pei, Hironori Waki, Karen Reue, Peter Tontonoz, Nico Mitro, Damien C. Wilpitz, and Kye Won Park
- Subjects
Physiology ,medicine.drug_class ,Phenotypic screening ,HUMDISEASE ,Regulator ,Enzyme-Linked Immunosorbent Assay ,Pharmacology ,Biology ,Article ,Cell Line ,Mice ,chemistry.chemical_compound ,Harmine ,medicine ,Animals ,Humans ,Thiazolidinedione ,Luciferases ,Receptor ,Molecular Biology ,DNA Primers ,Adipogenesis ,Wnt signaling pathway ,Calorimetry, Indirect ,Cell Biology ,Small molecule ,Mice, Inbred C57BL ,PPAR gamma ,Adipose Tissue ,Gene Expression Regulation ,chemistry ,Signal Transduction - Abstract
PPARgamma is the master regulator of adipogenesis and the molecular target of the thiazolidinedione antidiabetic drugs. By screening for compounds that promote adipogenesis, we identified a small molecule that targets the PPARgamma pathway by a distinct mechanism. This molecule, harmine, is not a ligand for the receptor; rather, it acts as a cell-type-specific regulator of PPARgamma expression. Administration of harmine to diabetic mice mimics the effects of PPARgamma ligands on adipocyte gene expression and insulin sensitivity. Unlike thiazolidinediones, however, harmine does not cause significant weight gain or hepatic lipid accumulation. Molecular studies indicate that harmine controls PPARgamma expression through inhibition of the Wnt signaling pathway. This work validates phenotypic screening of adipocytes as a promising strategy for the identification of bioactive small molecules and suggests that regulators of PPARgamma expression may represent a complementary approach to PPARgamma ligands in the treatment of insulin resistance.
- Published
- 2007
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.