Intestinal epithelia regulate barrier integrity when challenged by inflammation, oxidative stress, and microbes. Transforming growth factor-β1 (TGF-β1) is a cytokine with known beneficial effects on intestinal epithelia, including barrier enhancement, after exposure to proinflammatory cytokines and infectious agents. The aim of this study was to determine whether TGF-β1 directly protects intestinal epithelia during hypoxia-reoxygenation (HR). Intestinal epithelial monolayers (T84, Caco-2) were exposed to either hypoxia (1% O2, 1 h) or oxidative stress (hydrogen peroxide, 1 mM), followed by normoxic atmosphere for different time points in the absence and presence of varying concentrations of TGF-β1. Transepithelial electrical resistance (TER) assessed barrier function, with RNA extracted for reverse transcription polymerase chain reaction analysis of GPx-1, HIF-1, heme-oxygenase-1 (HO-1), and NOX-1. In some experiments, intestinal epithelia were exposed to enterohemorrhagic Escherichia coli (EHEC) O157:H7 during the reoxygenation period and TER recorded 7 h after the infectious challenge. Hypoxia-reoxygenation significantly decreased TER in intestinal epithelia compared with normoxic controls. Transforming growth factor-β1 pretreatment ameliorated HR-induced epithelial barrier dysfunction in T84 (at 1 - 3 h) and Caco-2 (1 h) monolayers. Transforming growth factor-β1 preserved barrier integrity for up to 16 h after challenge with hydrogen peroxide. In TGF-β1-treated epithelial monolayers, only HO-1 mRNA significantly increased after HR (P < 0.05 vs. normoxic controls). The EHEC-induced epithelial barrier dysfunction was significantly worsened by intestinal HR (P < 0.05 vs. normoxia-EHEC-infected cells), but this was not protected by TGF-β1 pretreatment. Transforming growth factor-β1 preserves loss of epithelial barrier integrity caused by the stress of HR via a mechanism that may involve the upregulation of HO-1 transcription. Targeted treatment with TGF-β could lead to novel therapies in enteric diseases characterized by HR injury.
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http://dx.doi.org/10.1097/SHK.0000000000000333 | DOI Listing |
Curr Protein Pept Sci
January 2025
Galgotias College of Pharmacy, Pharmacy, Greater Noida, Uttar Pradesh, 201310, India.
In recent years, novel therapeutic approaches have revolutionized the landscape of medicine, offering promising avenues for the cure of various diseases. The novel approaches explore advancements in gene therapy in pharmaceuticals, immunotherapy, RNA-based therapeutics, cell-based therapies, and targeted tumor therapies. Gene therapy has emerged as a groundbreaking approach, leveraging genetic material to cure or prevent diseases by targeting defective genes.
View Article and Find Full Text PDFWorld J Gastroenterol
January 2025
Department of Internal Medicine, Mixed Hospital of Laghouat, Laghouat Faculty of Medicine, Amar Telidji University, Laghouat 03000, Algeria.
Liver cancer remains a significant global health challenge, characterized by high incidence and mortality rates. Despite advancements in medical treatments, the prognosis for liver cancer patients remains poor, highlighting the urgent need for novel therapeutic approaches. Traditional Chinese medicine (TCM), particularly (CB), has shown promise in addressing this need due to its multi-target therapeutic mechanisms.
View Article and Find Full Text PDFFront Bioeng Biotechnol
January 2025
Department of Urology, Beilun People's Hospital, Ningbo, Zhejiang, China.
Renal ischemia-reperfusion (IR) induces tissue hypoxia, resulting in disrupted energy metabolism and heightened oxidative stress. These factors contribute to tubular cell damage, which is a leading cause of acute kidney injury (AKI) and can progress to chronic kidney disease (CKD). The excessive generation of reactive oxygen species (ROS) plays a crucial role in the pathogenesis of AKI.
View Article and Find Full Text PDFPostepy Dermatol Alergol
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Department of Dermatology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.
Introduction: Systemic sclerosis is a complex disease characterized by the fibrosis and vasculopathy.
Aim: We aimed to assess scleroderma by examining involucrin, an early terminal differentiation marker of epidermal keratinocytes.
Material And Methods: Immunolocalization of involucrin was performed in healthy controls and patients with scleroderma lesions by using an immunofluorescence (IF) assay.
J Med Biochem
November 2024
University of Belgrade, Faculty of Medicine, University Clinical Centre of Serbia, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Belgrade.
Background: Previous studies suggested an important role of impairments in T cell subsets in different stages during type 1 diabetes (T1D) development, while data regarding CD25high T cells and transforming growth factor b1 (TGFβ1), both T regulatory associated, remains controversial. We analyzed the level of (a) CD25high T cells (b) TGFβ1 in 17 first-degree relatives of patients with T1D in stage 1 (FDRs1) (GADA+, IA-2+); 34 FDRs in stage 0 (FDRs0) (GADA, IA-2); 24 recent-onset T1D in insulin-requiring state (IRS); 10 patients in clinical remission (CR); 18 healthy, unrelated controls (CTR).
Methods: T cell subsets were characterized by two-color immunofluorescence staining and flow cytometry; TGFβ1 was determined by ELISA, GADA, and IA-2 by RIA.
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