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Last update 23 Jan 2025

ITGA6

Last update 23 Jan 2025

Basic Info

Synonyms

Alpha6p, CD49 antigen-like family member F, CD49f

+ [8]

Introduction

Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (By similarity). Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464).

Drugs associated with ITGA6

RD-Cy7 fluorophore

Target

ITGA6

Mechanism

ITGA6 antagonists [+1]

Active Org.

Institute of Automation Chinese Academy of Sciences

Originator Org.

Institute of Automation Chinese Academy of Sciences

Active Indication

Hepatocellular Carcinoma

Inactive Indication-

Drug Highest PhasePhase 1

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

[18F]AlF-NOTA-A6P

Target

ITGA6

Mechanism

ITGA6 antagonists

Active Org.

Jiangxi Nuoyu Pharmaceutical Co., Ltd. [+1]

Originator Org.

Jiangxi Nuoyu Pharmaceutical Co., Ltd. [+1]

Active Indication

Colorectal Cancer

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

P5G-10

Target

ITGA6

Mechanism

ITGA6 antagonists

Active Org.-

Originator Org.

Fred Hutchinson Cancer Research Center

Active Indication-

Inactive Indication-

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Clinical Trials associated with ITGA6

NCT06204835

/ RecruitingPhase 1IIT

ITGA6 Targeting NIR-II Fluorescence Image Guided Surgery of HCC Patients

In this study, the investigators will detect hepatocellular carcinoma lesions using fluoescence imaging with ITGA6 targeting probes during tumor resection surgery. The aim is to evaluate wether intraoperative fluorescence imaging targeting ITGA6 can help to improve the detction effect of hepatocellular carcinoma, and finally help the accurate surgical resection.
The main purposes of this study include:
To raise the detection rate of hepatocellular carcinoma intraoperatively using the novel NIR-II fluorescence molecular imaging and the ITGA6 targeting probe.
To validate the safety and effectiveness of the proposed ITGA6 targeting probes for clinical application.

Start Date07 Jan 2024

Sponsor / Collaborator

Institute of Automation Chinese Academy of Sciences

100 Clinical Results associated with ITGA6

100 Translational Medicine associated with ITGA6

0 Patents (Medical) associated with ITGA6

1,837

Literatures (Medical) associated with ITGA6

01 Feb 2025·Journal of Hepatology

Identification and functional validation of miR-190b-5p and miR-296-3p as novel therapeutic attenuators of liver fibrosis

Article

Author: Li, Ruomeng ; Möbus, Selina ; Bantel, Heike ; Wedemeyer, Heiner ; Khanal, Rajendra ; Büning, Hildegard ; Peng, Qi ; Singh, Manvendra K. ; Cantz, Tobias ; Markovic, Jovana ; Vondran, Florian W R ; Singh, Manvendra K ; Sharma, Amar Deep ; Engel, Bastian ; Balakrishnan, Asha ; Yuan, Qinggong ; Vondran, Florian W.R. ; Taubert, Richard ; Ott, Michael

BACKGROUND & AIMSLiver fibrosis and its end-stage form cirrhosis contribute to millions of deaths annually. The lack of robust antifibrotic molecules is in part attributed to the absence of any functional screens to identify molecular regulators using patient-derived primary human hepatic myofibroblasts, which are key drivers of fibrosis.METHODSHere, to identify robust regulators of fibrosis, we performed functional microRNA screenings in primary human hepatic myofibroblasts followed by in vivo validation in three independent mouse models of fibrosis (toxin, cholestasis and MASH).RESULTSWe identified miR-190b-5p and miR-296-3p as robust antifibrotic miRNAs that suppress liver fibrosis. Notably, the expression of miR-190b-5p and miR-296-3p was found to be significantly reduced in human livers with fibrosis. Mechanistically, we discovered hyaluronan synthase 2 (HAS2) and integrin alpha-6 (ITGA6) as novel targets of miR-190b-5p and miR-296-3p, respectively. Furthermore, we demonstrated that the antifibrotic properties of miR-190b-5p and miR-296-3p are, at least in part, dependent on HAS2 and ITGA6. Finally, we showed the antifibrotic function of both miRNAs in a human liver bud model, which mimics multiple features of the human liver.CONCLUSIONSCollectively, in our study we discovered miR-190b-5p and miR-296-3p as two novel antifibrotic miRNAs, and that HAS2 and ITGA6 contribute to miR-190b-5p- and miR-296-3p-mediated inhibition of liver fibrosis. These results provide a foundation for future research to explore the clinical utility of miR-190b-5p and miR-296-3p in fibrosis.IMPACT AND IMPLICATIONSLiver fibrosis and cirrhosis contribute to millions of deaths worldwide and remain unmet medical needs. In this study, we discovered two microRNAs, miR-190b-5p and miR-296-3p, which suppress liver fibrosis in preclinical mouse models and a human liver bud model. Our promising results encourage further studies that aim to develop both miRNAs for the treatment of liver fibrosis in patients.

01 Feb 2025·eBioMedicine

Epithelial stem cells from human small bronchi offer a potential for therapy of idiopathic pulmonary fibrosis

Article

Author: Jiang, Rong ; Shan, Shan ; Zhong, Cheng ; Liu, Zeyu ; Dai, Haotian ; Huang, Moli ; Zhang, Jingyuan ; Li, Chunwei ; Xu, Yongle ; Yu, Ruize ; Gu, Xiaohua ; Hong, Yue ; Zheng, Qi ; Xu, Feng ; Ren, Tao ; Li, Zhoubin

BACKGROUNDIdiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial pneumonia with restrictive ventilation. Recently, the structural and functional defects of small airways have received attention in the early pathogenesis of IPF. This study aimed to elucidate the characteristics of small airway epithelial dysfunction in patients with IPF and explore novel therapeutic interventions to impede IPF progression by targeting the dysfunctional small airways.METHODSAirway trees spanning the proximal-distal axis were harvested from control lungs and explanted lungs with end-stage IPF undergoing transplant. Qualified basal cells (BCs, p63/Krt5/ITGA6/NGFR) were expanded, and their cellular functions, feasibility, safety and efficacy for transplantation therapy in IPF were validated with experiments in vitro and mouse model. Single-cell RNA-sequencing was employed to elucidate the underlying mechanisms governing the BCs based therapy. Based upon these evidences, three patients with advanced IPF and small airway dysfunction received autologous-BCs transplantation. Post-transplantation assessments included lung function, exercise capacity and high resolution computed tomography (HRCT) scans were analyzed to quantify the clinical benefits conferred by the BCs transplantation.FINDINGSAn overall landscape of senescent phenotype in airway epithelial cells and airway stem/progenitor cells along the proximal-distal axis of the airway tree in IPF were outlined. In contrast to the cells situated in distal airways, BCs located in small bronchi in IPF displayed a non-senescent phenotype, with comparable proliferative, differentiative capabilities, and similar transcriptomic profiles to normal controls. In a mouse model of pulmonary fibrosis, BCs exhibited promising protective efficacy and safety for transplantation therapy. Autologous BCs transplantation in three advanced IPF patients with small airway dysfunction yielded significant clinical improvements in pulmonary function, particularly evidence in lung volume and small airway function.INTERPRETATIONEpithelia of small bronchi in IPF contain functional and expandable basal stem cells, which exert therapeutic benefits via bronchoscopic implantation. Our findings offer a potential for IPF treatment by targeting small airways.FUNDINGNational Natural Science Foundation of China (82430001, 81930001, and 81900059), Shanghai Shenkang Hospital Development Center (SHDC2020CR3063B), Department of Science and Technology of Shandong Province (2024HWYQ-058).

01 Feb 2025·International Journal of Radiation Oncology*Biology*Physics

Using Integrin αvβ6-Targeted Positron Emission Tomography Imaging to Longitudinally Monitor Radiation-Induced Pulmonary Fibrosis In Vivo

Article

Author: Robinson, Clifford G. ; Klaas, Amanda ; Bergom, Carmen ; Boas, Cristian W Villas ; Robinson, Clifford G ; Lo, William C.Y. ; Huynh, Truc T ; Samson, Pamela ; Rogers, Buck E ; Rogers, Buck E. ; Boas, Cristian W. Villas ; Huynh, Truc T. ; Grogan, Felicia ; Strong, Lori ; Lo, William C Y

PURPOSERadiation-induced pulmonary fibrosis (RIPF) is a potentially serious and disabling late complication of radiation therapy. Monitoring RIPF progression is challenging due to the absence of early detection tools and the difficulty in distinguishing RIPF from other lung diseases using standard imaging methods. In the lungs, integrin αvβ6 is crucial in the development of RIPF, acting as a significant activator of transforming growth factor β after radiation injury. This study aimed to investigate integrin α_vβ₆-targeted positron emission tomography (PET) imaging ([⁶⁴Cu]Cu-α_vβ₆-BP) to study RIPF development in vivo.METHODS AND MATERIALSWe used a focal RIPF model (70 Gy delivered focally to a 3 mm spot in the lung) and a whole lung RIPF model (14 Gy delivered to the whole lung) in adult C57BL/6J mice. Small animal PET/computed tomography images were acquired 1 hour postinjection of 11.1 MBq of [⁶⁴Cu]Cu-α_vβ₆-BP. Animals were imaged for 8 weeks in the focal RIPF model and 6 months in the whole lung RIPF model. Immunohistochemistry for integrin α_vβ₆ and trichrome staining were performed.RESULTSIn the focal RIPF model, there was focal uptake of [⁶⁴Cu]Cu-α_vβ₆-BP in the irradiated region at week 4 that progressively increased at weeks 6 and 8. In the whole lung RIPF model, minimal uptake of the probe was observed at 4 months post-radiation therapy, which significantly increased at months 5 and 6. Expression of integrin α_vβ₆ was validated histologically by immunohistochemistry in both models.CONCLUSIONSIntegrin α_vβ₆-targeted PET imaging using [⁶⁴Cu]Cu-α_vβ₆-BP can serve as a useful tool to identify RIPF in vivo.

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ITGA6

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