Pannexin1: Role as a Sensor to Injury Is Attenuated in Pretype 2 Corneal Diabetic Epithelium

Epithelial wound healing is essential to repair the corneal barrier function after injury and requires coordinated epithelial sheet movement over the wounded region. The presence and role of pannexin1 on multilayered epithelial sheet migration was examined in unwounded and wounded corneal epithelium from C57BL/6J (B6) control and diet-induced obese (DiO) mice, a pretype 2 diabetic model. We hypothesize that pannexin1 is dysregulated, and the interaction of two ion-channel proteins (P2X7 and pannexin1) is altered in pretype 2 diabetic tissue. Pannexin1 was found to be present along cell borders in unwounded tissue, and no significant difference was observed between DiO and B6 control. However, an epithelial debridement induced a striking difference in pannexin1 localization. The B6 control epithelium displayed intense staining near the leading edge, which is the region where calcium mobilization was detected, whereas the staining in the DiO corneal epithelium was diffuse and lacked distinct gradation in intensity back from the leading edge. Cells distal to the wound in the DiO tissue were irregular in shape, and the morphology was similar to that of epithelium inhibited with 10Panx, a pannexin1 inhibitor. Pannexin1 inhibition reduced mobilization of calcium between cells near the leading edge, and MATLAB scripts revealed a reduction in cell-cell communication that was also detected in cultured cells. Proximity ligation was performed to determine if P2X7 and pannexin1 interaction was a necessary component of motility and communication. While there was no significant difference in the interaction in unwounded DiO and B6 control corneal epithelium, there was significantly less interaction in the wounded DiO corneas both near the wound and back from the edge. The results demonstrate that pannexin1 contributes to the healing response, and P2X7 and pannexin1 coordination may be a required component of cell-cell communication and an underlying reason for the lack of pathologic tissue migration.

Download Full-text

The predicting roles of carcinoembryonic antigen and its underlying mechanism in the progression of coronavirus disease 2019

Critical Care ◽

10.1186/s13054-021-03661-y ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Runzhi Huang ◽

Tong Meng ◽

Qiongfang Zha ◽

Kebin Cheng ◽

Xin Zhou ◽

...

Keyword(s):

Retrospective Study ◽

Cell Communication ◽

Underlying Mechanism ◽

Prognostic Indicators ◽

Type Ii ◽

Potential Mechanism ◽

Type Ii Pneumocyte ◽

Type Ii Pneumocytes ◽

Significant Difference ◽

Cell Cell

Abstract Background The coronavirus disease 2019 (COVID-19) has induced a worldwide epidemiological event with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known. Objective The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism. Methods The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively. Results In total, 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P < 0.001) and multivariate analysis (P = 0.020). The scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of CEA in lungs and peripherals, respectively. The results revealed the potential roles of CEA were significantly distributed in type II pneumocytes of BALF and developing neutrophils of PBMCs, participating in the progression of COVID-19 by regulating the cell–cell communication. Conclusion This study identifies the prognostic roles of CEA in COVID-19 patients and implies the potential roles of CEACAM8-CEACAM6 in the progression of COVID-19 by regulating the cell–cell communication of developing neutrophils and type II pneumocyte.

Download Full-text

Corneal Epithelial–Stromal Fibroblast Constructs to Study Cell–Cell Communication in Vitro

Bioengineering ◽

10.3390/bioengineering6040110 ◽

2019 ◽

Vol 6 (4) ◽

pp. 110 ◽

Cited By ~ 4

Author(s):

Tina B. McKay ◽

Dimitrios Karamichos ◽

Audrey E. K. Hutcheon ◽

Xiaoqing Guo ◽

James D. Zieske

Keyword(s):

Wound Healing ◽

Basement Membrane ◽

Extracellular Vesicles ◽

Corneal Epithelium ◽

Cell Communication ◽

Corneal Wound Healing ◽

Corneal Epithelial ◽

Matrix Deposition ◽

Corneal Wound ◽

Cell Cell

Cell–cell communication plays a fundamental role in mediating corneal wound healing following injury or infection. Depending on the severity of the wound, regeneration of the cornea and the propensity for scar development are influenced by the acute resolution of the pro-fibrotic response mediated by closure of the wound via cellular and tissue contraction. Damage of the corneal epithelium, basement membrane, and anterior stroma following a superficial keratectomy is known to lead to significant provisional matrix deposition, including secretion of fibronectin and thrombospondin-1, as well as development of a corneal scar. In addition, corneal wounding has previously been shown to promote release of extracellular vesicles from the corneal epithelium, which, in addition to soluble factors, may play a role in promoting tissue regeneration. In this study, we report the development and characterization of a co-culture system of human corneal epithelial cells and corneal stromal fibroblasts cultured for 4 weeks to allow extracellular matrix deposition and tissue maturation. The secretion of provisional matrix components, as well as small and large extracellular vesicles, was apparent within the constructs, suggesting cell–cell communication between epithelial and stromal cell populations. Laminin-1β was highly expressed by the corneal epithelial layer with the presence of notable patches of basement membrane identified by transmission electron microscopy. Interestingly, we identified expression of collagen type III, fibronectin, and thrombospondin-1 along the epithelial–stromal interface similar to observations seen in vivo following a keratectomy, as well as expression of the myofibroblast marker, α-smooth muscle actin, within the stroma. Our results suggest that this corneal epithelial–stromal model may be useful in the study of the biochemical phenomena that occur during corneal wound healing.

Download Full-text

The Drosophila Afadin and ZO-1 homologues Canoe and Polychaetoid act in parallel to maintain epithelial integrity when challenged by adherens junction remodeling

Molecular Biology of the Cell ◽

10.1091/mbc.e19-04-0209 ◽

2019 ◽

Vol 30 (16) ◽

pp. 1938-1960 ◽

Cited By ~ 15

Author(s):

Lathiena A. Manning ◽

Kia Z. Perez-Vale ◽

Kristina N. Schaefer ◽

Mycah T. Sewell ◽

Mark Peifer

Keyword(s):

Cultured Cells ◽

Adherens Junction ◽

Leading Edge ◽

Cell Junctions ◽

Epithelial Integrity ◽

Tissue Integrity ◽

Mammalian Homologue ◽

Cell Intercalation ◽

Actomyosin Cytoskeleton ◽

Cell Cell

During morphogenesis, cells must change shape and move without disrupting tissue integrity. This requires cell–cell junctions to allow dynamic remodeling while resisting forces generated by the actomyosin cytoskeleton. Multiple proteins play roles in junctional–cytoskeletal linkage, but the mechanisms by which they act remain unclear. Drosophila Canoe maintains adherens junction–cytoskeletal linkage during gastrulation. Canoe’s mammalian homologue Afadin plays similar roles in cultured cells, working in parallel with ZO-1 proteins, particularly at multicellular junctions. We take these insights back to the fly embryo, exploring how cells maintain epithelial integrity when challenged by adherens junction remodeling during germband extension and dorsal closure. We found that Canoe helps cells maintain junctional–cytoskeletal linkage when challenged by the junctional remodeling inherent in mitosis, cell intercalation, and neuroblast invagination or by forces generated by the actomyosin cable at the leading edge. However, even in the absence of Canoe, many cells retain epithelial integrity. This is explained by a parallel role played by the ZO-1 homologue Polychaetoid. In embryos lacking both Canoe and Polychaetoid, cell junctions fail early, with multicellular junctions especially sensitive, leading to widespread loss of epithelial integrity. Our data suggest that Canoe and Polychaetoid stabilize Bazooka/Par3 at cell–cell junctions, helping maintain balanced apical contractility and tissue integrity.

Download Full-text

The predicting roles of carcinoembryonic antigen and its underlying mechanism in the progression of coronavirus disease 2019

10.21203/rs.3.rs-125433/v1 ◽

2020 ◽

Author(s):

Runzhi Huang ◽

Tong Meng ◽

Qiongfang Zha ◽

Kebin Cheng ◽

Xin Zhou ◽

...

Keyword(s):

Retrospective Study ◽

Cell Communication ◽

Underlying Mechanism ◽

Prognostic Indicators ◽

Type Ii ◽

Potential Mechanism ◽

Type Ii Pneumocyte ◽

Type Ii Pneumocytes ◽

Significant Difference ◽

Cell Cell

Abstract Background The coronavirus disease 2019 (COVID-19) has induced a worldwide pneumonia with a high infectivity and mortality. However, the predicting biomarkers and their potential mechanism in the progression of COVID-19 are not well known. Objective The aim of this study is to identify the candidate predictors of COVID-19 and investigate their underlying mechanism. Methods The retrospective study was conducted to identify the potential laboratory indicators with prognostic values of COVID-19 disease. Then, the prognostic nomogram was constructed to predict the overall survival of COVID-19 patients. Additionally, the scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of the most important prognostic indicators in lungs and peripherals, respectively. Results 304 hospitalized adult COVID-19 patients in Wuhan Jinyintan Hospital were included in the retrospective study. CEA was the only laboratory indicator with significant difference in the univariate (P < 0.001) and multivariate analysis (P = 0.021). The scRNA-seq data of BALF and PBMCs from COVID-19 patients were downloaded to investigate the underlying mechanism of CEA in lungs and peripherals, respectively. The results revealed the potential roles of CEA were significantly distributed in Type II pneumocytes of BALF and developing neutrophils of PBMCs, participating in the progression of COVID-19 by regulating the cell-cell communication. Conclusion This study identifies the prognostic roles of CEA in COVID-19 patients and implies the potential roles of CEACAM8-CEACAM6 in the progression of COVID-19 by regulating the cell-cell communication of developing neutrophils and Type II pneumocyte.

Download Full-text

The Drosophila Afadin and ZO-1 homologs Canoe and Polychaetoid act in parallel to maintain epithelial integrity when challenged by adherens junction remodeling

10.1101/609123 ◽

2019 ◽

Author(s):

Lathiena A. Manning ◽

Kia Z. Perez-Vale ◽

Kristina N. Schaefer ◽

Mycah T. Sewell ◽

Mark Peifer

Keyword(s):

Cultured Cells ◽

Adherens Junction ◽

Leading Edge ◽

Cell Junctions ◽

Dorsal Closure ◽

Epithelial Integrity ◽

Tissue Integrity ◽

Cell Intercalation ◽

Actomyosin Cytoskeleton ◽

Cell Cell

AbstractDuring morphogenesis cells must change shape and move without disrupting tissue integrity. This requires cell-cell junctions to allow dynamic remodeling while resisting force generated by the actomyosin cytoskeleton. Multiple proteins play roles in junctional-cytoskeletal linkage, but the mechanisms by which they act remain unclear. Drosophila Canoe maintains adherens junction-cytoskeletal linkage during gastrulation. Canoe’s mammalian homolog Afadin plays similar roles in cultured cells, working in parallel with ZO-1 proteins, particularly at multicellular junctions. We took these insights back into the fly embryo, exploring how cells maintain epithelial integrity when challenged by adherens junction remodeling during germband extension and dorsal closure. We found Canoe helps cells maintain junctional-cytoskeletal linkage when challenged by the junctional remodeling inherent in mitosis, cell intercalation and neuroblast invagination, or by forces generated by the actomyosin cable at the leading edge. However, even in the absence of Canoe many cells retain epithelial integrity. This is explained by a parallel role played by the ZO-1 homolog Polychaetoid. In embryos lacking both Canoe and Polychaetoid, cell junctions fail early, with multicellular junctions especially sensitive, leading to widespread loss of epithelial integrity. Our data suggest Canoe and Polychaetoid stabilize Bazooka/Par3 at cell-cell junctions, helping maintain balanced apical contractility and tissue integrity.

Download Full-text

Validating a conceptual framework for the core concept of “cell-cell communication”

AJP Advances in Physiology Education ◽

10.1152/advan.00100.2016 ◽

2017 ◽

Vol 41 (2) ◽

pp. 260-265 ◽

Cited By ~ 8

Author(s):

Joel Michael ◽

Patricia Martinkova ◽

Jenny McFarland ◽

Ann Wright ◽

William Cliff ◽

...

Keyword(s):

Conceptual Framework ◽

Cell Communication ◽

Core Concept ◽

The Core ◽

Significant Difference ◽

Different Types ◽

Institutional Types ◽

Four Levels ◽

Main Ideas ◽

Cell Cell

We have created and validated a conceptual framework for the core physiology concept of “cell-cell communication.” The conceptual framework is composed of 51 items arranged in a hierarchy that is, in some instances, four levels deep. We have validated it with input from faculty who teach at a wide variety of institutional types. All items making up the framework were deemed essential to moderately important. However, some of the main ideas were clearly judged to be more important than others. Furthermore, the lower in the hierarchy an item is, the less important it is thought to be. Finally, there was no significant difference in the ratings given by faculty at different types of institutions.

Download Full-text