BACKGROUNDDelayed wound healing is a serious complication of diabetic wounds, posing a significant challenge to the treatment of patients with diabetes. Diabetic wound healing is a complex dynamic process involving angiogenesis and inflammatory responses. Currently, there are limited targeted therapies to promote diabetic wound healing. This study aimed to reveal the role of CLEC14A in the process of diabetic wound healing, with the hope of identifying new therapeutic targets to accelerate the healing of diabetic wounds.METHODSIn vivo, diabetic mice were generated by combined streptozotocin (STZ) and high-fat diet treatment. The wound healing model was established in wild-type and Clec14a^-/- diabetic mice. The degree of wound healing, as well as angiogenesis and inflammation during the healing process, were evaluated through Hematoxylin and Eosin (H&E) staining, immunohistochemical staining, and immunofluorescence staining. In vitro, the angiogenic activities of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed following treatment with high glucose and adenoviruses overexpressing CLEC14A, using scratch assays and tube formation assays. Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were utilized to evaluate the levels of inflammation in HUVECs.RESULTSCLEC14A expression was suppressed in diabetic wounds. Deletion of the Clec14a inhibited angiogenesis and activated inflammatory responses in vivo. High-glucose treatment led to decreased CLEC14A expression, impaired angiogenic capacity, and elevated inflammatory levels in vitro. However, adenoviral-mediated overexpression of CLEC14A reversed the response induced by high glucose.CONCLUSIONCLEC14A accelerates diabetic wound healing by promoting angiogenesis and reducing wound inflammation.

01 May 2024·Angiogenesis

Group XIV C-type lectins: emerging targets in tumor angiogenesis

Review

Author: Vigil, Isaac ; Sun, Yi ; Schulick, Richard D ; Torphy, Robert J ; Zhu, Yuwen ; Yee, Elliott J

AbstractC-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology. Recently, group XIV CTLDs have been shown to play significant roles in cancer progression, namely tumor angiogenesis and metastatic dissemination. Interest in therapeutically targeting tumor vasculature is increasing and the search for novel angiogenic targets is ongoing. Group XIV CTLDs have emerged as key moderators of tumor angiogenesis and metastasis, thus offering substantial therapeutic promise for the clinic. Herein, we review our current knowledge of group XIV CTLDs, discuss each’s role in malignancy and associated potential therapeutic avenues, briefly discuss group XIV CTLDs in the context of two other relevant lectin families, and offer future direction in further elucidating mechanisms by which these proteins function and facilitate tumor growth.

01 Apr 2024·Insect Science

Alternative relay regulates the adenosine triphosphatase activity of Locusta migratoria striated muscle myosin

Article

Author: Li, Jing ; Li, Xiang-Dong ; Zhang, Ning ; Liu, Chang ; Qu, Mingbo ; Ni, Tong ; Hao, Jie

AbstractLocust (Locusta migratoria) has a single striated muscle myosin heavy chain (Mhc) gene, which contains 5 clusters of alternative exclusive exons and 1 differently included penultimate exon. The alternative exons of Mhc gene encode 4 distinct regions in the myosin motor domain, that is, the N‐terminal SH3‐like domain, one lip of the nucleotide‐binding pocket, the relay, and the converter. Here, we investigated the role of the alternative regions on the motor function of locust muscle myosin. Using Sf9‐baculovirus protein expression system, we expressed and purified 5 isoforms of the locust muscle myosin heavy meromyosin (HMM), including the major isoform in the thorax dorsal longitudinal flight muscle (FL1) and 4 isoforms expressed in the abdominal intersegmental muscle (AB1 to AB4). Among these 5 HMMs, FL1‐HMM displayed the highest level of actin‐activated adenosine triphosphatase (ATPase) activity (hereafter referred as ATPase activity). To identify the alternative region(s) responsible for the elevated ATPase activity of FL1‐HMM, we produced a number of chimeras of FL1‐HMM and AB4‐HMM. Substitution with the relay of AB4‐HMM (encoded by exon‐14c) substantially decreased the ATPase activity of FL1‐HMM, and conversely, the relay of FL1‐HMM (encoded by exon‐14a) enhanced the ATPase activity of AB4‐HMM. Mutagenesis showed that the exon‐14a‐encoded residues Gly474 and Asn509 are responsible for the elevated ATPase activity of FL1‐HMM. Those results indicate that the alternative relay encoded by exon‐14a/c play a key role in regulating the ATPase activity of FL1‐HMM and AB4‐HMM.

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

CLEC14A

Basic Info

Related

Analysis