AI Article Synopsis
Article Abstract
Metabolic syndrome is a significant worldwide public health challenge and is inextricably linked to adverse renal and cardiovascular outcomes. The inhibition of the transient receptor potential cation channel subfamily C member 6 (TRPC6) has been found to ameliorate renal outcomes in the unilateral ureteral obstruction (UUO) of accelerated renal fibrosis. Therefore, the pharmacological inhibition of TPRC6 could be a promising therapeutic intervention in the progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome. In the present study, we hypothesized that the novel selective TRPC6 inhibitor SH045 (larixyl N-methylcarbamate) ameliorates UUO-accelerated renal fibrosis in a New Zealand obese (NZO) mouse model, which is a polygenic model of metabolic syndrome. The in vivo inhibition of TRPC6 by SH045 markedly decreased the mRNA expression of pro-fibrotic markers (, , , , , ) and chemokines (, , ) in UUO kidneys of NZO mice compared to kidneys of vehicle-treated animals. Renal expressions of intercellular adhesion molecule 1 (ICAM-1) and α-smooth muscle actin (α-SMA) were diminished in SH045- versus vehicle-treated UUO mice. Furthermore, renal inflammatory cell infiltration (F4/80+ and CD4+) and tubulointerstitial fibrosis (Sirius red and fibronectin staining) were ameliorated in SH045-treated NZO mice. We conclude that the pharmacological inhibition of TRPC6 might be a promising antifibrotic therapeutic method to treat progressive tubulo-interstitial fibrosis in hypertension and metabolic syndrome.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224794 | PMC |
| http://dx.doi.org/10.3390/ijms23126870 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Systematic Review of the Molecular Mechanisms Involved in the Association Between PCOS and Endometrial and Ovarian Cancers.
J Cell Mol Med
December 2024
Biosciences Institute, Newcastle University Cancer Centre, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK.
Polycystic ovary syndrome (PCOS), a major cause of female infertility, affects 4%-20% of reproductive-age women. Metabolic and hormonal alterations are key features of PCOS, potentially raising the risk of endometrial (EC) and ovarian (OVCA) cancers. This systematic review aims to summarise the proposed molecular mechanisms involved in the association between PCOS and EC or OVCA.
View Article and Find Full Text PDFThe Role of Exercise in Steatotic Liver Diseases: An Updated Perspective.
Liver Int
January 2025
Depatrtment of Medicine, Karsh Division of Gastroenterology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Background: The increasing prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), parallels the rise in sedentary lifestyles. MASLD is the most common form of steatotic liver disease (SLD), which represents the umbrella beneath which the vast majority of chronic liver diseases fall, including alcohol-related liver disease and their overlap. These conditions are the leading contributors to chronic liver disease, significantly impacting global morbidity and mortality.
View Article and Find Full Text PDFWhole-exome sequencing identified a novel heterozygous variant in in a Chinese family with neurodevelopmental disorder characterized by impaired language, behavioral abnormalities, and dysmorphic facies.
Front Genet
December 2024
Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.
UBAP2L-deficiency syndrome, also known as neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies (NEDLBF, OMIM 620494), is an extremely rare autosomal dominant disorder. This condition is caused by heterozygous variant in the gene (NM_014847.4, MIM 616472), which encodes the ubiquitin-associated protein 2-like protein involved in the formation of stress granules (SGs).
View Article and Find Full Text PDFNeuropathy and the metabolic syndrome.
eNeurologicalSci
March 2025
Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA.
Obesity and the metabolic syndrome (MetS) are major global health challenges that contribute significantly to the rising prevalence of type 2 diabetes (T2D) and neuropathy. Neuropathy, a common and disabling complication of T2D, is characterized by progressive distal-to-proximal axonal degeneration, driven in part by mitochondrial dysfunction in both neurons and axons. Recent evidence points to the toxic effects of saturated fatty acids on peripheral nerve health, with studies demonstrating that these fats impair mitochondrial function and bioenergetics, leading to distal axonal loss.
View Article and Find Full Text PDFMultisystem clinicopathologic and genetic analysis of MELAS.
Orphanet J Rare Dis
December 2024
Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Zhongshan Road 321#, Nanjing, 210008, Jiangsu, China.
Background And Objectives: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a maternally inherited mitochondrial disorder that mostly affects the central nervous system and skeletal muscle. This study provides a comprehensive summary of the clinical symptoms, multisystemic pathogenesis, and genetic characteristics of MELAS syndrome. The aim was to improve comprehension of clinical practice and gain a deeper understanding of the latest pathophysiological theories.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!