Biology subjects

Huang, W.-J.

Publications and source records attributed to Huang, W.-J..

3 recordsLinked to original sources

bioRxiv2026

Stromal control of sympathetic rewiring in metastatic lymph nodes

Metastatic lymph nodes (LNs) are dynamically remodeled tissues, but this process has been understood mainly in immune and stromal terms. We show that tumor-driven LN remodeling also involves adaptive neural rewiring. In a mouse model of nodal metastasis, sympathetic fibers, but not sensory fibers, progressively expanded during LN remodeling and tracked with metastatic progression. Fibroblastic reticular cells (FRCs) adopted a neuro-supportive program characterized by increased hepatocyte growth factor (HGF) production, while local stromal HGF acted through MET on sympathetic neurons to stimulate neurite outgrowth. Increased substrate stiffness enhanced FRC activation and HGF production, suggesting that mechanical remodeling may reinforce the neuro-supportive stromal state. Inhibition of HGF signaling or ablation of sympathetic innervation reduced LN enlargement and nodal tumor burden. These findings identify neural plasticity as a functional component of the metastatic LN niche and reveal a stromal/mechanical/neural framework that supports metastatic LN progression.

cancer biology↗

bioRxiv2021

FGF21 Normalizes Plasma Glucose in Mouse Models of Type 1 Diabetes and Insulin Receptor Dysfunction

Fibroblast growth factor 21 (FGF21) is a member of the fibroblast growth factor (FGF) family of proteins. The biological activity of FGF21 was first shown to induce insulin independent glucose uptake in adipocytes through the GLUT1 transporter. Subsequently, it was shown to have effects on the liver to increase fatty acid oxidation. FGF21 treatment provides beneficial metabolic effects in both animal models and patients with obesity, type 2 diabetes mellitus (T2D) and/or fatty liver disease. In this paper, we revisited the original finding and found that insulin independent glucose uptake in adipocytes is preserved in the presence of an insulin receptor antagonist. Using a 40 kDa PEGylated (PEG) and half-life extended form of FGF21 (FGF21-PEG), we extended these in vitro results to two different mouse models of diabetes. FGF21-PEG normalized plasma glucose in streptozotocin-treated mice, a model of type 1 diabetes (T1D), without restoring pancreatic {beta}-cell function. FGF21-PEG also normalized plasma glucose levels and improved glucose tolerance in mice chronically treated with an insulin competitive insulin receptor antagonist, a model of autoimmune/Type-B insulin resistance. These data extend the pharmacological potential of FGF21 beyond the settings of T2D, fatty liver and obesity.

pharmacology and toxicology↗

bioRxiv2018

Propofol inhibits endogenous formyl peptide-induced neutrophil activation and alleviates lung injury

Critically ill patients have a high risk of sepsis. Various studies have demonstrated that propofol has anti-inflammatory effects that may benefit critically ill patients who require anesthesia. However, the mechanism and therapeutic effect remain incompletely understood. Our previous data suggest that propofol can act as a formyl peptide receptor 1 (FPR1) antagonist. Here, we hypothesize that propofol mitigates sepsis-induced acute lung injury (ALI) by inhibiting mitochondria-derived N-formyl peptide-mediated neutrophil activation. In human neutrophils, propofol competitively reduced the release of elastase, superoxide, and reactive oxygen species induced by fMMYALF, a human mitochondria-derived N-formyl peptide. In addition, propofol significantly inhibited fMMYALF-induced chemotaxis, calcium mobilization, and phosphorylation of protein kinase B and mitogen-activated protein kinases. These results indicate that propofol suppresses neutrophil activation by blocking the interaction between endogenous N-formyl peptide and its receptor, FPR1, thus inhibiting downstream signaling. Furthermore, propofol alleviated alveolar wall disruption, edematous changes, and neutrophil infiltration in lipopolysaccharide-induced ALI in mice. Noticeably, propofol improved the survival of sepsis mice. This study indicates that the anti-neutrophil effects of propofol may benefit critically ill septic patients.

pharmacology and toxicology↗