Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2(Akita) gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ∼30% to ∼200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor β1 (TGFβ1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFβ1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease.
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http://dx.doi.org/10.1073/pnas.1600511113 | DOI Listing |
Front Endocrinol (Lausanne)
November 2024
Wuxi Maternity and Child Health Care Hospital, Affiliated Women's Hospital of Jiangnan University, Wuxi, Jiangsu, China.
Introduction: The placental vascular system plays an important role in the development of pregnancy hypertension in preeclampsia. The gene profiles of whole placental tissue (containing blood vessels and many other structural components) and pure vascular tissue should be very different. All previous reports using RNA-seq analysis in the placenta have tested its whole tissue or the villous part, and thus the gene profiles in the pure placental blood vessels are unknown.
View Article and Find Full Text PDFDig Liver Dis
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Clinical Laboratory Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, China, 650101. Electronic address:
Background & Aims: Primary biliary cholangitis (PBC), a typical autoimmune liver disease, is characterized by an increased infiltration of immune cells. However, the specific molecular mechanisms regulating immune cell migration in PBC are unknown. Engulfment and cell motility 1 (ELMO1) plays an important function in cellular dynamics.
View Article and Find Full Text PDFGastroenterol Rep (Oxf)
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Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, P. R. China.
Background: Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD), which still lacks of reliable markers and therapeutic options. Cellular senescence has been considered an important mechanism of intestinal fibrosis, but the underlying molecular link remains elusive.
Methods: Tissues were stained using α-smooth muscle actin (α-SMA), fibronectin, and collagen I as markers of myofibroblastic differentiation.
Pathophysiology
November 2023
Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes autism, Asperger's syndrome, and pervasive developmental disorder. ASD is characterized by poor interpersonal relationships and strong attachment. The correlations between activated or inactivated gene products, which occur as a result of genetic mutations affecting neurons in ASD patients, and ASD symptoms are now of critical concern.
View Article and Find Full Text PDFAnn Dermatol
December 2023
Department of Dermatology, Soonchunhyang University Seoul Hospital, Seoul, Korea.
Background: Melanoma is one of the most aggressive and metastatic skin cancers. Although overexpression of Dock180 and Elmo1 has been identified in various cancers, including glioma, ovarian cancer, and breast cancer, their expression and functions in melanoma remain unknown.
Objective: This study aims to confirm the expression of Dock180 and Elmo1, their underlying mechanisms, and roles in melanoma.
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