Hepatocyte Growth Factor Suppresses Inflammation and Promotes Epithelium Repair in Corneal Injury

Abstract

Corneal injuries are among the major causes of ocular morbidity and vision impairment. Optimal epithelial wound healing is critical for the integrity and transparency of the cornea after injury. Hepatocyte growth factor (HGF) is a mitogen and motility factor that primarily regulates epithelial cell function. Herein, we investigate the effect of HGF on proliferation of corneal epithelial cells (CECs) in inflamed conditions both in vitro and in vivo. We demonstrate that HGF not only promotes CEC proliferation in homeostatic conditions but also reverses the anti-proliferative effect of the inflammatory environment on these cells. Furthermore, using a mouse model of ocular injury, we show that HGF treatment suppresses ocular inflammation and actively augments CEC proliferation, leading to improved and accelerated corneal epithelial repair. These findings have potential translational implications and could provide a framework for the development of novel HGF-based therapies for corneal epithelial defects.

Topical cell-free conditioned media harvested from adipose tissue-derived stem cells promote recovery from corneal epithelial defects caused by chemical burns

“…MMP9 is also inhibited by HGF because it is induced by inflammatory cytokines such as IL-1β 41 , 42 . The increases in IL-1β, VEGF, IL-6, and MMP9 levels were significantly less in the CT group than in the CB group during 1 to 3 days after the injury, which is also consistent with a recent study on HGF 37 . EGF expression was significantly elevated in the CT group compared with that in the CB group at 2 and 3 days after injury.…”

Topical cell-free conditioned media harvested from adipose tissue-derived stem cells promote recovery from corneal epithelial defects caused by chemical burns

“…MMP9 is also inhibited by HGF because it is induced by inflammatory cytokines such as IL-1β 41 , 42 . The increases in IL-1β, VEGF, IL-6, and MMP9 levels were significantly less in the CT group than in the CB group during 1 to 3 days after the injury, which is also consistent with a recent study on HGF 37 . EGF expression was significantly elevated in the CT group compared with that in the CB group at 2 and 3 days after injury.…”

Evaluation of the Regenerative Potential of Platelet-Lysate and Platelet-Poor Plasma Derived from the Cord Blood Units in Corneal Wound Healing Applications: An In Vitro Comparative Study on Corneal Epithelial Cells

“…Moreover, a series of events could follow, such as macrophage polarization (from M1 to M2) and activation of tolerogenic DCs. In parallel, M2 macrophage can further promote the tissue remodeling process, as has been reported in literature [42][43][44][45][46][47][48][49][50][51][52]. In the second phase, the growth factors of CB-PL induce the cell migration, proliferation, and production of tissue remodeling proteins such as collagen, syndecan, and perlecan, as has been described previously [66], promoting the healing process of the damaged cornea.…”

Cotransplantation of Limbal Epithelial and Stromal Cells for Ocular Surface Reconstruction

“…37 Hepatocyte growth factor secreted by MSCs in an inflammatory environment has been shown to suppress the conversion of stromal cells into fibroblasts after corneal injury. 30 Hepatocyte growth factor also was found to be expressed in both LSSCs and keratocytes in this study. It is possible that LSSCs and MSCs share similar gene expression profiles and cellular functions.…”

Topical cell-free conditioned media harvested from adipose tissue-derived stem cells promote recovery from corneal epithelial defects caused by chemical burns

“…MMP9 is also inhibited by HGF because it is induced by inflammatory cytokines such as IL-1β 41 , 42 . The increases in IL-1β, VEGF, IL-6, and MMP9 levels were significantly less in the CT group than in the CB group during 1 to 3 days after the injury, which is also consistent with a recent study on HGF 37 . EGF expression was significantly elevated in the CT group compared with that in the CB group at 2 and 3 days after injury.…”

Evaluation of the Regenerative Potential of Platelet-Lysate and Platelet-Poor Plasma Derived from the Cord Blood Units in Corneal Wound Healing Applications: An In Vitro Comparative Study on Corneal Epithelial Cells

“…Moreover, a series of events could follow, such as macrophage polarization (from M1 to M2) and activation of tolerogenic DCs. In parallel, M2 macrophage can further promote the tissue remodeling process, as has been reported in literature [42][43][44][45][46][47][48][49][50][51][52]. In the second phase, the growth factors of CB-PL induce the cell migration, proliferation, and production of tissue remodeling proteins such as collagen, syndecan, and perlecan, as has been described previously [66], promoting the healing process of the damaged cornea.…”

Cotransplantation of Limbal Epithelial and Stromal Cells for Ocular Surface Reconstruction

“…37 Hepatocyte growth factor secreted by MSCs in an inflammatory environment has been shown to suppress the conversion of stromal cells into fibroblasts after corneal injury. 30 Hepatocyte growth factor also was found to be expressed in both LSSCs and keratocytes in this study. It is possible that LSSCs and MSCs share similar gene expression profiles and cellular functions.…”

Topical cell-free conditioned media harvested from adipose tissue-derived stem cells promote recovery from corneal epithelial defects caused by chemical burns

“…MMP9 is also inhibited by HGF because it is induced by inflammatory cytokines such as IL-1β 41 , 42 . The increases in IL-1β, VEGF, IL-6, and MMP9 levels were significantly less in the CT group than in the CB group during 1 to 3 days after the injury, which is also consistent with a recent study on HGF 37 . EGF expression was significantly elevated in the CT group compared with that in the CB group at 2 and 3 days after injury.…”

Evaluation of the Regenerative Potential of Platelet-Lysate and Platelet-Poor Plasma Derived from the Cord Blood Units in Corneal Wound Healing Applications: An In Vitro Comparative Study on Corneal Epithelial Cells

“…Moreover, a series of events could follow, such as macrophage polarization (from M1 to M2) and activation of tolerogenic DCs. In parallel, M2 macrophage can further promote the tissue remodeling process, as has been reported in literature [42][43][44][45][46][47][48][49][50][51][52]. In the second phase, the growth factors of CB-PL induce the cell migration, proliferation, and production of tissue remodeling proteins such as collagen, syndecan, and perlecan, as has been described previously [66], promoting the healing process of the damaged cornea.…”

Cotransplantation of Limbal Epithelial and Stromal Cells for Ocular Surface Reconstruction

“…37 Hepatocyte growth factor secreted by MSCs in an inflammatory environment has been shown to suppress the conversion of stromal cells into fibroblasts after corneal injury. 30 Hepatocyte growth factor also was found to be expressed in both LSSCs and keratocytes in this study. It is possible that LSSCs and MSCs share similar gene expression profiles and cellular functions.…”