Keratinocyte growth factor (KGF) induces podosome formation via integrin-Erk1/2 signaling in human immortalized oral epithelial cells

Sa, Guoliang; Liu, Zhikang; Ren, Jian‐Gang; Wan, Qiang; Xiong, Xiaolin; Yu, Zi‐Li; Chen, Heng; Zhao, Yi‐Fang; He, Shaokun

doi:10.1016/j.cellsig.2019.05.007

Cited by 10 publications

(5 citation statements)

References 35 publications

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“…It has previously been reported that LPS activates a series of signaling transduction pathways, including ERK, which serves crucial roles in inflammation (25). In the present study, the expression levels and phosphorylation status of ERK1/2 were analyzed in EpCs and MPs; however, the current results revealed that LPS had no effect on the expression levels or phosphorylation status of ERK1/2 in EpC/MP co-culture, which may be because the phosphorylation of ERK1/2 occurred at an earlier stage (39). Although there is no direct evidence to date, it was hypothesized that the interaction between co-cultured EpCs and MPs may affect ERK1/2 expression.…”

Section: Discussioncontrasting

confidence: 58%

Mechanisms of the lipopolysaccharide‑induced inflammatory response in alveolar epithelial cell/macrophage co‑culture

Qin

Chen

et al. 2020

Exp Ther Med

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The interaction between alveolar epithelial cells (EpCs) and macrophages (MPs) serves an important role in initiating and maintaining inflammation in chronic pulmonary diseases. The aim of the present study was to investigate the molecular mechanisms of the inflammatory response in co-cultured EpCs and MPs. Briefly, a co-culture system of A549 (EpCs) and THP-1 (monocyte/MPs) cells was established in a filter-separated Transwell plate to evaluate the inflammatory response.

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Section: Discussioncontrasting

confidence: 58%

Mechanisms of the lipopolysaccharide‑induced inflammatory response in alveolar epithelial cell/macrophage co‑culture

Qin

Chen

et al. 2020

Exp Ther Med

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“…Like our findings, KGF-mediated differentiation of adipose-derived stem cells toward keratinocytes was demonstrated with an increased expression of the supra-basal and terminal keratinocyte genes, CK10 and Involucrin, respectively . ERK1/2 and AKT have been demonstrated as the major downstream effectors in KGF/FGFR2IIIB signaling , which correlates with our observation of activated of STAT3, ERK1/2, and AKT in regulating the transdifferentiation of MSCs toward KLCs.…”

Section: Discussionsupporting

confidence: 91%

3D Porous Polymer Scaffold-Conjugated KGF-Mimetic Peptide Promotes Functional Skin Regeneration in Chronic Diabetic Wounds

Choudhury,

Madhu Krishna,

Sen

et al. 2024

ACS Appl. Mater. Interfaces

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The re-epithelialization process gets severely dysregulated in chronic nonhealing diabetic foot ulcers/wounds. Keratinocyte growth factor (KGF or FGF-7) is the major modulator of the re-epithelialization process, which regulates the physiological phenotypes of cutaneous keratinocytes. The existing therapeutic strategies of growth factor administration have several limitations. To overcome these, we have designed a KGF-mimetic peptide (KGFp, 13mer) based on the receptor interaction sites in murine KGF. KGFp enhanced migration and transdifferentiation of mouse bone marrow-derived MSCs toward keratinocyte-like cells (KLCs). A significant increase in the expression of skin-specific markers Bnc1 (28.5-fold), Ck5 (14.6-fold), Ck14 (26.1-fold), Ck10 (187.7-fold), and epithelial markers EpCam (23.3-fold) and Cdh1 (64.2-fold) was associated with the activation of ERK1/2 and STAT3 molecular signaling in the KLCs. Further, to enhance the stability of KGFp in the wound microenvironment, it was conjugated to biocompatible 3D porous polymer scaffolds without compromising its active binding sites followed by chemical characterization using Fourier transform infrared spectroscopy, field-emission scanning electron microscopy, dynamic mechanical analysis, and thermogravimetry. In vitro evaluation of the KGFp-conjugated 3D polymer scaffolds revealed its potential for transdifferentiation of MSCs into KLCs. Transplantation of allogeneic MSC GFP using KGFp-conjugated 3D polymer scaffolds in chronic nonhealing type 2 diabetic wounds (db/db transgenic, 50−52 weeks old male mice) significantly enhanced re-epithelialization-mediated wound closure rate (79.3%) as compared to the control groups (Untransplanted −22.4%, MSC GFP -3D polymer scaffold −38.5%). Thus, KGFp-conjugated 3D porous polymer scaffolds drive the fate of the MSCs toward keratinocytes that may serve as potential stem cell delivery platform technology for tissue engineering and transplantation.

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“…The processes involved in the assembly of these structures share many similarities. Depending on the cell type, the sequential process of podosome/invadopodium assembly can be initiated by cell adhesion via integrins [87], vascular endothelial growth factor (VEGF) [88], platelet-derived growth factor (PDGF) [89], transforming growth factor beta (TGFβ) [90], keratinocyte growth factor (KGF) [91], colony-stimulating factor-1 (CSF-1) [92], or EGF-derived [93] signals. Upon receptor tyrosine kinase activation, the non-receptor c-SRC kinase becomes active and phosphorylates several substrates, including the TKS proteins, cortactin, N-WASP, focal adhesion kinase (FAK), and other signaling molecules [94,95].…”

Section: Molecular Organizers Of Podosome and Invadopodium Assemblymentioning

confidence: 99%

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

Kudlik

Takács

Radnai

et al. 2020

IJMS

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Scaffold proteins are typically thought of as multi-domain “bridging molecules.” They serve as crucial regulators of key signaling events by simultaneously binding multiple participants involved in specific signaling pathways. In the case of epidermal growth factor (EGF)-epidermal growth factor receptor (EGFR) binding, the activated EGFR contacts cytosolic SRC tyrosine-kinase, which then becomes activated. This process leads to the phosphorylation of SRC-substrates, including the tyrosine kinase substrates (TKS) scaffold proteins. The TKS proteins serve as a platform for the recruitment of key players in EGFR signal transduction, promoting cell spreading and migration. The TKS4 and the TKS5 scaffold proteins are tyrosine kinase substrates with four or five SH3 domains, respectively. Their structural features allow them to recruit and bind a variety of signaling proteins and to anchor them to the cytoplasmic surface of the cell membrane. Until recently, TKS4 and TKS5 had been recognized for their involvement in cellular motility, reactive oxygen species-dependent processes, and embryonic development, among others. However, a number of novel functions have been discovered for these molecules in recent years. In this review, we attempt to cover the diverse nature of the TKS molecules by discussing their structure, regulation by SRC kinase, relevant signaling pathways, and interaction partners, as well as their involvement in cellular processes, including migration, invasion, differentiation, and adipose tissue and bone homeostasis. We also describe related pathologies and the established mouse models.

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Keratinocyte growth factor (KGF) induces podosome formation via integrin-Erk1/2 signaling in human immortalized oral epithelial cells

Cited by 10 publications

References 35 publications

Mechanisms of the lipopolysaccharide‑induced inflammatory response in alveolar epithelial cell/macrophage co‑culture

Mechanisms of the lipopolysaccharide‑induced inflammatory response in alveolar epithelial cell/macrophage co‑culture

3D Porous Polymer Scaffold-Conjugated KGF-Mimetic Peptide Promotes Functional Skin Regeneration in Chronic Diabetic Wounds

Advances in Understanding TKS4 and TKS5: Molecular Scaffolds Regulating Cellular Processes from Podosome and Invadopodium Formation to Differentiation and Tissue Homeostasis

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