Biology subjects

YIN, J.

Publications and source records attributed to YIN, J..

3 recordsLinked to original sources

bioRxiv2026

B3GNT7 regulates mucin glycosylation and protects against colitis and infection

Mucus covers and protects colonic epithelial cells. Mucus is mainly composed of heavily O-glycosylated proteins called mucins, and disruption of normal mucin glycosylation occurs in ulcerative colitis (UC). Mucin-2 (MUC2) is the major colonic mucin, and MUC2 O-glycans are often extended with sulfated polyLacNAc, also known as keratan sulfate (KS). The GlcNAc residues in KS are added by B3GNT family members. B3GNT7 is highly expressed in the colon, and B3GNT7 expression is dramatically reduced in UC. However, the function of B3GNT7 in colonic physiology is unexplored. Here we show that B3gnt7 is a key player in colonic physiology through its function in controlling the structure of mucus glycans. We found that B3GNT7 prefers to extend a sulfated acceptor substrate and is required for production of polyLacNAc-modified mucus in a human goblet cell model. In vivo, B3GNT7 regulates Muc2, Muc13, and Muc17 O-glycosylation. Intestinal B3GNT7 deficiency increases susceptibility to colitis and enteric infection in mice, showing that B3GNT7-dependent glycosylation confers protective properties to colonic mucus. Taken together, these results demonstrate that B3GNT7 has a function distinct from other B3GNT family members and is critical for maintaining colonic homeostasis. SIGNIFICANCE STATEMENTUlcerative colitis is a chronic inflammatory bowel disease that affects 5 million people globally. The colonic mucus layer forms a protective barrier over colonic epithelial cells and is disrupted in ulcerative colitis. Mucus is composed of mucin proteins decorated by carbohydrates, called glycans. Glycans confer protective properties to the mucus barrier, and mucin glycans change in ulcerative colitis. B3GNT7 is an enzyme that elongates glycans and is downregulated in ulcerative colitis. In this study, we use in vitro and in vivo models to demonstrate that B3GNT7 regulates colonic mucus glycans and protects mice against colitis and infection. Our findings provide molecular insight into the contributions of B3GNT7-dependent glycans to colonic homeostasis.

biochemistry↗

bioRxiv2026

Lipid mobilization establishes metabolic tolerance and prevents autonomic collapse in infection

Survival during infection depends on both pathogen clearance and the ability to tolerate infection-induced physiological changes. Metabolic adaptations are a central component of this tolerance, but the mechanisms underlying these responses remain incompletely defined. Here, we identify white adipose tissue (WAT) lipolysis as a central regulator of metabolic tolerance to infection. In patients with sepsis, higher circulating non-esterified fatty acid (NEFA) levels were associated with reduced mortality. In mouse models of polymicrobial sepsis, infection induced robust adipose lipolysis and increased circulating NEFAs. Genetic ablation of adipose triglyceride lipase (ATGL) in adipose tissue impaired lipolysis, leading to hypothermia, bradycardia, and increased mortality without altering immune cell populations or pathogen burden, consistent with a defect in tolerance rather than resistance. Mechanistically, lipolysis-derived NEFAs, but not glycerol, were required for protection, as restoring circulating NEFAs rescued autonomic stability and survival in adipose tissue ATGL-deficient mice. Infection-induced lipolysis was redundantly regulated and did not depend on any single upstream signaling pathway. Both pharmacologic activation of lipolysis using a {beta}3-adrenergic agonist and exogenous fatty acid supplementation increased circulating NEFAs, improved survival, and promoted tolerance in mice. Consistent with these findings, analysis of real-world electronic health record data demonstrated that septic patients receiving FDA-approved {beta}3-adrenergic agonists had reduced mortality or hospice discharge in a propensity-matched cohort. Together, these results identify WAT lipolysis and circulating fatty acids as key mediators of tolerance to infection and support a therapeutic strategy based on repurposing clinically available {beta}3-adrenergic agonists to improve outcomes in sepsis. One Sentence SummaryWhite adipose tissue lipolysis promotes metabolic tolerance to infection through circulating fatty acids and is associated with improved survival in sepsis

physiology↗

bioRxiv2024

Initiation of Lumen Formation from Junctions via Differential Actomyosin Contractility Regulated by Dynamic Recruitment of Rasip1

Vascular lumens are essential for the dispersal of nutrients, oxygen, and immune cells throughout the body. De novo lumen formation necessitates the precise segregation of junctional proteins from apical surfaces. Direct visualization of this process and a comprehensive understanding on how the apical and junctional compartments are segregated and established remain elusive, due to the lack of visualizable systems, proper reporters and manipulative tools. Using zebrafish as an experimental model, we have established a wealth of molecular reporters, photo-convertible and optogenetic tools and combined them with genetic analyses to study the establishment of apical domains from pre-apical junctional complexes. Our study identified Rasip1 as one of the earliest apical proteins recruited, peripheralizing cortical contractility at the junctional patches by inhibiting NMII at the center, thereby initiating the outward flow of junctional complexes. After the establishment of the apical compartments, Rasip1 shuttles between junctions and the apical compartments to the high-tension sites and tunes down the local hyper contractility, restricting Cdh5 to junctions by suppressing apical contractility. Above all, the formation of de novo lumens and maintenance of junctional integrity depend on the precise control of contractility within the apical compartments and junctions, orchestrated by the dynamic recruitment of Rasip1.

developmental biology↗