Last update 01 Nov 2024

KRT8

Last update 01 Nov 2024

Basic Info

Synonyms

CARD2, CK-8, CK8

+ [10]

Introduction

Together with KRT19, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle.

Drugs associated with KRT8

CN115028720

Patent Mining

Target

KRT8

Mechanism-

Active Org.

Jiangsu Jinbaiye Machinery Manufacturing Co., Ltd. [+1]

Originator Org.

Jiangsu Jinbaiye Machinery Manufacturing Co., Ltd. [+1]

Active Indication

Neoplasms [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

MR-022

Target

DOCK8 x KRT8

Mechanism

DOCK8 inhibitors [+1]

Active Org.-

Originator Org.

Centre Léon Bérard Lyon et Rhône-Alpes

Active Indication-

Inactive Indication

Colorectal Cancer

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with KRT8

100 Translational Medicine associated with KRT8

0 Patents (Medical) associated with KRT8

2,027

Literatures (Medical) associated with KRT8

01 Jan 2025·Gene

Differentiation of human umbilical cord mesenchymal stem cells into functional intestinal epithelial cells via conditioned medium co-culture

Article

Author: Li, Menglong ; Hu, Jiale ; Wang, Zhiqiang ; Qu, Huaidong ; Li, Man ; Zhang, Xianglian ; Liang, Rui

BACKGROUNDThe induction of stem cell differentiation to generate intestinal epithelial cells (IECs) with absorptive functions offers significant therapeutic potential for treating conditions such as Crohn's disease, ulcerative colitis, radiation enteritis, and other refractory intestinal epithelial injuries. Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of differentiating into functional IEC-like cells.OBJECTIVEThis study aimed to induce the differentiation of hUC-MSCs into IECs using a conditioned medium co-culture method.METHODA culture medium derived from human IECs was used as the inductive medium to facilitate the differentiation of hUC-MSCs into IECs. The cellular morphology was assessed using inverted microscopy, and the expression of IEC markers, including Villin, CK20, CK8, and CK18 proteins, was analyzed via immunofluorescence staining. Furthermore, the expression levels of IEC markers, such as KRT18, were quantified using real-time quantitative PCR analysis. The functionality of the differentiated IECs in terms of sucrase secretion was assessed through sucrase activity assays.RESULTSBy the 14th day of induction, hUC-MSCs exhibited a morphology similar to IECs and exhibited the expression of IEC markers, including the KRT18 gene and Villin, CK20, CK8, and CK18 proteins. Sucrase activity assays further confirmed that the differentiated cells demonstrated significant sucrase activity.CONCLUSIONThe conditioned medium co-culture method effectively induced the differentiation of hUC-MSCs into functional IECs.

01 Oct 2024·Journal of Allergy and Clinical Immunology

Role of DOCK8 in Cytokine Storm Syndromes

Article

Author: Canna, Scott W ; Walter, Mark R ; Gordon, Scott M. ; Atkinson, T. Prescott ; Behrens, Edward M. ; Cron, Randy Q ; Cron, Randy Q. ; Gordon, Scott M ; Behrens, Edward M ; Kreiger, Portia A. ; Eloseily, Esraa M. ; Chu, Niansheng ; Weiser, Peter ; Cron, Remy R ; Canna, Scott W. ; Walter, Mark R. ; Kreiger, Portia A ; Cron, Remy R. ; Atkinson, T Prescott ; Nguyen, Junior ; Zhang, Mingce ; Eloseily, Esraa M

BACKGROUNDCytokine storm syndromes (CSS), including hemophagocytic lymphohistiocytosis (HLH), are increasingly recognized as hyperinflammatory states leading to multi-organ failure and death. Familial HLH (FHL) in infancy results from homozygous genetic defects in perforin-mediated cytolysis by CD8 T-lymphocytes and natural killer (NK) cells. Later onset CSS are frequently associated with heterozygous defects in FHL genes, but genetic etiologies for most are unknown. We identified rare DOCK8 variants in CSS patients.OBJECTIVEWe explore the role of CSS patient-derived DOCK8 mutations on cytolytic activity in NK cells. We further study effects of DOCK8 deficiency in murine models of CSS.METHODSDOCK8 cDNA from 2 unrelated CSS patients with different missense mutations were introduced into human NK-92 NK cells by foamy virus transduction. NK cell degranulation (CD107a), cytolytic activity against K562 target cells, and interferon-gamma (IFNγ) production were explored by flow cytometry. A third CSS patient DOCK8 mRNA splice acceptor site variant was explored by exon trapping. Dock8^-/- mice were assessed for features of CSS (weight loss, splenomegaly, hepatic inflammation, cytopenias, and IFNγ levels) upon challenge with lymphocytic choriomeningitis virus (LCMV) and excess IL-18.RESULTSBoth patient DOCK8 missense mutations decreased cytolytic function in NK cells in a partial dominant-negative fashion in vitro. The patient DOCK8 splice variant disrupted mRNA splicing in vitro. LCMV infection promoted CSS in Dock8^-/- mice and interacted with excess IL-18 limiting T-cell numbers while promoting CD8 T-cell hyperactivation.CONCLUSIONMutations in DOCK8 may contribute to CSS-like hyperinflammatory states by altering cytolytic function in a threshold model of disease.

01 Oct 2024·Laboratory Investigation

Impact of Keratins 8 and 18 Genetic Variants on the Severity of Alcoholic Liver Disease

Article

Author: Rubbia-Brandt, Laura ; Lin-Marq, Nathalie ; Elkrief, Laure ; Spahr, Laurent ; Berney, Thierry ; Tihy, Matthieu

Alcohol-related liver disease (ALD) affects ∼30% of heavy drinkers and is characterized by liver steatosis, fibrosis, and steatohepatitis. The aggregation of keratins 8 (KRT8) and 18 (KRT18) plays a key role in the formation of Mallory-Denk bodies, a hallmark of ALD. Circulating levels of KRT18 fragments are elevated during ALD, and several KRT8/18 genetic variants have been linked to an increased risk of liver disease. In this study, we explored the relationship between the histologic features of ALD and genetic variants of KRT8/18 in 106 severe patients with ALD from the Hôpitaux Universitaires de Genève. We found a significant over-representation of several KRT8 (rs2070910, rs137898974, rs1065306) and KRT18 (rs17120866, rs1492241) variants located in the noncoding regions of these genes. Increased circulating level of keratins 18 fragments were associated with rs17120866 and alcoholic hepatitis. The combination of several KRT18 variants appeared associated with a poorer prognosis. These results highlight the possible role of KRT18 variants in ALD.

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KRT8

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