Background: Elevated circulating IgA complex deposits in the glomerular mesangium and causes resultant mesangial cell activation, eventually leading to the progression of IgA nephropathy (IgAN). Complement-C1q TNF-related protein 3 (CTRP3) is documented as a potential anti-inflammatory and anti-fibrotic mediator; however, its role in IgAN is unknown.
Methods: Serum polymeric IgA (pIgA) was isolated from patients with IgAN and healthy volunteers. Human mesangial cells (HMCs) were incubated with the isolated pIgA. The expression of CTRP3 and its effects on inflammatory cytokines and extracellular matrix were evaluated.
Results: Median circulating CTRP3 decreased in patients with IgAN compared to the controls, accompanied by the elevated serum and urine TGF-β and IL-6. While urine CTRP3 in IgAN patients were comparable to that in healthy subjects. pIgA dose-dependently inhibited the expression of CTRP3 and HMC tolerated pIgA at 1.0 mg/ml, for which galactose-deficient IgA might be responsible. pIgA markedly increased IL-6 and TGF-β in HMCs, which were suppressed after Ad-CTRP3 transfection. Additionally, CTRP3 significantly inhibited pIgA-stimulated HMC proliferation, cell cycle progression and synthesis of CTGF and fibronectin. Furthermore, we found that pIgA-treated HMC exhibited higher NF-954;B activity as reflected by the increased levels of nuclear p65. Moreover, Src activation and the subsequent Smad3 phosphorylation were significantly elevated in response to the stimulation with pIgA. However, NF-954;B activity and Smad3 signaling were inhibited after Ad-CTRP3 transfection in HMC.
Conclusion: CTRP3 potentially targeted to NF-954;B and TGF-β-Src-Smad3 signaling and exerted anti-inflammatory and anti-fibrotic roles to attenuate the progression of IgAN, which may represent a new strategy for the treatment of IgAN.
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http://dx.doi.org/10.1159/000446353 | DOI Listing |
Rev Assoc Med Bras (1992)
January 2025
Applied Cellular and Molecular Research Center, Kerman University of Medical Sciences - Kerman, Iran.
Objective: Coronary artery bypass graft surgery is one of the most frequently performed surgeries worldwide. Coronary artery bypass graft surgery induces an inflammatory response. Interleukin-8 is a pro-inflammatory cytokine that plays a role in the pathogenesis of cardiovascular diseases.
View Article and Find Full Text PDFBMC Endocr Disord
December 2024
Department of Biochemistry, Faculty of Medicine, Iran University of Medical Sciences, P.O. Box: 1449614525, Tehran, Iran.
Biomol Biomed
March 2024
Department of Hepatic Surgery and Liver Transplantation Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou, China.
Identifying the precise moment before the onset of hepatocellular carcinoma (HCC) remains a significant challenge in the medical field. The existing biomarkers fall short of pinpointing the critical point preceding HCC formation. This study aimed to determine the exact tipping point for the transition from cirrhosis to HCC, identify the core Dynamic Network Biomarker (DNB), and elucidate its regulatory effects on HCC.
View Article and Find Full Text PDFJ Psychiatr Res
April 2024
Department of Clinical Laboratory, Wuhan Pulmonary Hospital, Baofeng Road, Qiaokou District, Wuhan, 430030, China. Electronic address:
Background: The adipokines secreted by adipocytes might play an important role through crossing the blood brain barrier to the brain, which could mediate the common physiological pathway between depression and obesity. CTRP4, a member of the CTRP family, is highly expressed in human adipose tissue and brain tissue.
Objective: this study aimed to measure serum C1q/TNF-related protein 4 (CTRP4) levels in depressive patients to explore the association between CTRP4 levels and depression.
J Am Heart Assoc
February 2024
Department of Cardiology Fuwai Hospital, Chinese Academy of Medical Sciences (Shenzhen Sun Yat-Sen Cardiovascular Hospital) Shenzhen China.
Background: This study investigated whether gCTRP9 (globular C1q/tumor necrosis factor-related protein-9) could restore high-glucose (HG)-suppressed endothelial progenitor cell (EPC) functions by activating the endothelial nitric oxide synthase (eNOS).
Methods And Results: EPCs were treated with HG (25 mmol/L) and gCTRP9. Migration, adhesion, and tube formation assays were performed.
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