Zhuo Xu1, Chunsun Dai1. 1. Center for Kidney Disease, Second Affiliated Hospital, Nanjing Medical University, Nanjing, China.
Abstract
BACKGROUND: Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes. However, the role and mechanisms of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further investigation. METHODS: In this study, a mouse model with fibroblast-specific FGFR2 gene disruption was generated. The knockouts were born normal and no kidney dysfunction or histological abnormality was found within 2 months after birth. A kidney ischemia/reperfusion injury (IRI) model was created. RESULTS: Kidney fibrosis was developed in the control littermates within 2 and 4 weeks after IRI, while in the knockouts, total collagen deposition, fibronectin, and alpha smooth muscle actin expression were decreased compared to those in the control littermates. In addition, the numbers of Ki-67-positive interstitial cells as well as TUNEL-positive interstitial cells were lower in the knockout kidneys at 4 weeks after IRI. Phosphorylated extracellular regulated protein kinase 1/2 was decreased in the knockout kidneys at 2 and 4 weeks after IRI compared to those in the control littermates. CONCLUSION: These results suggest that FGF/FGFR2 signaling may promote the proliferation and activation of kidney fibroblasts, which contribute to the development of kidney fibrosis.
BACKGROUND: Fibroblast growth factors (FGFs) are heparin-binding proteins involved in a variety of biological processes. However, the role and mechanisms of FGF/FGFR2 signaling in fibroblast activation and kidney fibrosis need further investigation. METHODS: In this study, a mouse model with fibroblast-specific FGFR2 gene disruption was generated. The knockouts were born normal and no kidney dysfunction or histological abnormality was found within 2 months after birth. A kidney ischemia/reperfusion injury (IRI) model was created. RESULTS: Kidney fibrosis was developed in the control littermates within 2 and 4 weeks after IRI, while in the knockouts, total collagen deposition, fibronectin, and alpha smooth muscle actin expression were decreased compared to those in the control littermates. In addition, the numbers of Ki-67-positive interstitial cells as well as TUNEL-positive interstitial cells were lower in the knockout kidneys at 4 weeks after IRI. Phosphorylated extracellular regulated protein kinase 1/2 was decreased in the knockout kidneys at 2 and 4 weeks after IRI compared to those in the control littermates. CONCLUSION: These results suggest that FGF/FGFR2 signaling may promote the proliferation and activation of kidney fibroblasts, which contribute to the development of kidney fibrosis.
Authors: Francesco Borgia; Lucia Peterle; Paolo Custurone; Mario Vaccaro; Giovanni Pioggia; Sebastiano Gangemi Journal: Int J Mol Sci Date: 2022-03-17 Impact factor: 5.923