Author: Wu, Lei ; DiPersio, Mathieu R. ; Duarte, Giesse Albeche ; Dhulipalla, Sanjana ; Longmate, Whitney M ; DiPersio, C. Michael ; Lamar, John M. ; Longmate, Whitney M. ; DiPersio, C Michael ; Lamar, John M ; DiPersio, Mathieu R

To date, studies of the role for epidermal integrin α3β1 in cutaneous wound re-epithelialization have produced conflicting results: wound studies in skin from global α3-null neonatal mice have implicated the integrin in promoting timely wound re-epithelialization, whereas studies in adult mice with constitutive, epidermal-specific α3β1 deletion have not. The objective of this study was to utilize a model of inducible α3β1 deletion in the epidermis to clarify the role of α3β1 in the healing of adult wounds. We utilized the recently developed transgenic K14^Cre-ERT::α3^flx/flx mice (ie, inducible α3 epidermal knockout), permitting us to delete floxed Itga3 alleles (α3^flx/flx) from epidermis just prior to wounding with topical treatment of 4-hydroxytamoxifen. This allows for the elucidation of α3β1-dependent wound healing in adult skin, free from compensatory mechanisms that may occur after embryonic deletion of epidermal α3β1 in the widely used constitutive α3β1-knockout mouse. We found that re-epithelializing wound gaps are larger in inducible α3 epidermal knockout mice than in control mice, indicating delayed healing, and that epidermal integrin α3β1 promotes healing of wounds, at least in part by enhancing keratinocyte proliferation. This work provides essential rationale for future studies to investigate integrin α3β1 as a therapeutic target to facilitate wound healing.

01 Oct 2024·Science of The Total Environment

Mechanism underlying the role of integrin α3β1 in adhesive dysfunction between thyroid cells induced by diesel engine exhaust particles

Article

Author: Han, Wei ; Jiang, Menghui ; Mu, Chaohui ; Guo, Xiaoyin ; Li, Yanting ; Zheng, Yuxin ; Tang, Siying ; Piao, Jinmei ; Zhang, Hongna ; Jiang, Qixiao

The role and mechanisms of DEP exposure on thyroid injury are not yet clear. This study explores thyroid damage induced by in vivo DEP exposure using a mouse model. This study has observed alterations in thyroid follicular architecture, including rupture, colloid overflow, and the formation of voids. Additionally, there was a significant decrease in the expression levels of proteins involved in thyroid hormone synthesis, such as thyroid peroxidase and thyroglobulin, their trend of change is consistent with the damage to the thyroid structure. Serum levels of triiodothyronine and tetraiodothyronine were raise. However, the decrease in TSH expression suggests that the function of the HPT axis is unaffected. To delve deeper into the intrinsic mechanisms of thyroid injury, we performed KEGG pathway enrichment analysis, which revealed notable alterations in the cell adhesion signaling pathway. Our immunofluorescence results show that DEP exposure impairs thyroid adhesion, and integrin α3β1 plays an important role. CD151 binds to α3β1, promoting multimolecular complex formation and activating adhesion-dependent small GTPases. Our in vitro model has confirmed the pivotal role of integrin α3β1 in thyroid cell adhesion, which may be mediated by the CD151/α3β1/Rac1 pathway. In summary, exposure to DEP disrupts the structure and function of the thyroid, a process that likely involves the regulation of cell adhesion through the CD151/α3β1/Rac1 pathway, leading to glandular damage.

18 Sep 2024·Journal of the American Chemical Society

Development of Integrin-Facilitated Bispecific Aptamer Chimeras for Membrane Protein Degradation

Article

Author: Tan, Weihong ; Xie, Wanlin ; Li, Ling ; Qu, Fengli ; Sun, Weidi ; Liu, Yuan ; Zhang, Hui ; Ma, Lele ; Dang, Yang

The emergence of lysosome-targeting chimeras (LYTACs), which represents a promising strategy for membrane protein degradation based on lysosomal pathways, has attracted much attention in disease intervention and treatment. However, the expression level of commonly used lysosome-targeting receptors (LTRs) varies in different cell lines, thus limiting the broad applications of LYTACs. To overcome this difficulty, we herein report the development of integrin α3β1 (ITGA3B1)-facilitated bispecific aptamer chimeras (ITGBACs) as a platform for the degradation of membrane proteins. ITGBACs consist of two aptamers, one targeting ITGA3B1 and another binding to the membrane-associated protein of interest (POI), effectively transporting the POI into lysosomes for degradation. Our findings demonstrate that ITGBACs effectively eliminate pathological membrane proteins, such as CD71 and PTK7, inducing significant cell-cycle arrest and apoptosis and markedly inhibiting tumor growth in tumor-bearing mice models. Therefore, this work provides a novel and versatile membrane protein degradation platform, offering a promising targeted therapy based on tumor-specific LTRs.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

α3β1

Basic Info

Related

Analysis