Related Experiment Video
Updated: May 11, 2026
09:07
Dissection of Xenopus laevis Neural Crest for in vitro Explant Culture or in vivo Transplantation
Published on: March 5, 2014
Neu differentiation factor upregulates epidermal migration and integrin expression in excisional wounds
D M Danilenko1, B D Ring, J Z Lu
1Department of Experimental Pathology, Amgen, Inc., Thousand Oaks, California 91320-1789.
The Journal of Clinical Investigation
|February 1, 1995
Summary
Neu differentiation factor-alpha 2 (NDF-alpha 2) significantly enhances epidermal migration and proliferation in wound healing. This study demonstrates NDF-alpha 2
Area of Science:
- Cell Biology
- Dermatology
- Regenerative Medicine
Background:
- Neu differentiation factor (NDF) is a glycoprotein in the epidermal growth factor (EGF) family, known to bind HER-3 or HER-4 receptors and indirectly induce HER-2/neu phosphorylation.
- Multiple NDF isoforms exist due to alternative splicing, but their in vivo biological activities remain largely uncharacterized.
- NDF, HER-2/neu, and HER-3 are present in skin, and EGF family members influence keratinocyte behavior, suggesting a potential role for NDF in skin repair.
Purpose of the Study:
- To investigate the in vivo effects of NDF isoforms on epidermal migration and proliferation in a rabbit ear excisional wound model.
- To determine if NDF-alpha 2 can stimulate key cellular processes involved in cutaneous tissue repair.
Main Methods:
- Recombinant human NDF-alpha 2 (rhNDF-alpha 2) was applied once to rabbit ear wounds.
- Epidermal migration and thickness were measured.
- Expression of integrins (alpha 5, alpha 6) and differentiation markers (cytokeratin 10, filaggrin) was assessed in neoepidermis; HER-2/neu and HER-3 expression patterns were analyzed in wounded and unwounded skin.
Main Results:
- rhNDF-alpha 2 significantly increased epidermal migration and thickness at doses of 4-40 micrograms/cm2, while other tested isoforms (rhNDF-alpha 1, rhNDF-beta 1, rhNDF-beta 2) showed no effect.
- rhNDF-alpha 2 treatment led to increased neoepidermal expression of alpha 5/alpha 6 integrins and differentiation markers cytokeratin 10 and filaggrin.
- Endogenous NDF-alpha isoforms were found in dermal fibroblasts, while HER-2/neu and HER-3 were expressed in unwounded epidermis and adnexa; HER-2/neu decreased in wound neoepidermis, whereas HER-3 was upregulated.
Conclusions:
- NDF-alpha 2 is a potent stimulator of epidermal migration and proliferation in vivo, suggesting a significant role in wound healing.
- NDF-alpha 2 influences the expression of key molecules involved in epidermal repair, including integrins and differentiation markers.
- These findings propose that endogenous NDF-alpha 2 acts as a paracrine mediator in cutaneous tissue repair, directing initial epidermal migration.
Related Concept Videos
01:09Cell Migration
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
01:19Cell Migration
Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
01:12Renewal of Skin Epidermal Stem Cells
The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells,...
01:19Clinical Applications of Epidermal Stem Cells
Epidermal stem cells (EpiSCs) are mainly located at the basal layer of the epidermis. These cells repair minor injuries of the skin and replace dead skin cells. However, EpiSCs’ cannot heal severe wounds such as major burns or those from diabetes or hereditary disorders. In such cases, culturing the epidermal stem cells from the patient is possible and has yielded successful treatment options, such as laboratory-grown skin grafts. These grafts are synthesized using a patient’s own EpiSCs...
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...