Xiaoyi Yu1, Andrei Radulescu, Chun-Liang Chen, Iyore O James, Gail E Besner. 1. Department of Pediatric Surgery, Center for Perinatal Research, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, Ohio, USA.
Abstract
BACKGROUND: We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes angiogenesis and preserves mesenteric microvascular blood flow in several models of intestinal injury. The current study was designed to evaluate the effect of HB-EGF on pericytes, since these cells function to regulate capillary blood flow and new capillary growth. MATERIALS AND METHODS: C3H/10T1/2 mouse mesenchymal cells were differentiated into pericyte-like cells in vitro using transforming growth factor-β1 (TGF-β1). In addition, primary pericyte cultures were established from rat brain. The effect of HB-EGF on pericyte proliferation was assessed. In addition, cells were stressed by exposure to anoxia, and apoptosis determined. In vivo, we examined the effect of HB-EGF on pericytes in a model of intestinal I/R injury based on superior mesenteric artery occlusion (SMAO) in mice. RESULTS: Differentiated C3H/10T1/2 cells (pericyte-like cells) demonstrated morphologic characteristics of pericytes, and expressed pericyte specific markers. Addition of HB-EGF led to significant cell proliferation in differentiated pericyte-like cells, even under conditions of anoxic stress. Addition of the EGF receptor inhibitor AG 1478 led to complete inhibition of the proliferative effects of HB-EGF on pericyte-like cells. In addition, HB-EGF protected pericyte-like cells from anoxia-induced apoptosis. In addition, HB-EGF promoted cell proliferation in primary pericyte cultures. In vivo, administration of HB-EGF to mice subjected to intestinal I/R injury led to protection of pericytes from injury. CONCLUSIONS: These results suggest that HB-EGF may function as a microcirculatory blood flow regulator, at least in part, via its effects on pericytes.
BACKGROUND: We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes angiogenesis and preserves mesenteric microvascular blood flow in several models of intestinal injury. The current study was designed to evaluate the effect of HB-EGF on pericytes, since these cells function to regulate capillary blood flow and new capillary growth. MATERIALS AND METHODS: C3H/10T1/2mouse mesenchymal cells were differentiated into pericyte-like cells in vitro using transforming growth factor-β1 (TGF-β1). In addition, primary pericyte cultures were established from rat brain. The effect of HB-EGF on pericyte proliferation was assessed. In addition, cells were stressed by exposure to anoxia, and apoptosis determined. In vivo, we examined the effect of HB-EGF on pericytes in a model of intestinal I/R injury based on superior mesenteric artery occlusion (SMAO) in mice. RESULTS: Differentiated C3H/10T1/2 cells (pericyte-like cells) demonstrated morphologic characteristics of pericytes, and expressed pericyte specific markers. Addition of HB-EGF led to significant cell proliferation in differentiated pericyte-like cells, even under conditions of anoxic stress. Addition of the EGF receptor inhibitor AG 1478 led to complete inhibition of the proliferative effects of HB-EGF on pericyte-like cells. In addition, HB-EGF protected pericyte-like cells from anoxia-induced apoptosis. In addition, HB-EGF promoted cell proliferation in primary pericyte cultures. In vivo, administration of HB-EGF to mice subjected to intestinal I/R injury led to protection of pericytes from injury. CONCLUSIONS: These results suggest that HB-EGF may function as a microcirculatory blood flow regulator, at least in part, via its effects on pericytes.
Authors: Erika Iivanainen; Lassi Nelimarkka; Varpu Elenius; Satu-Maria Heikkinen; Teemu T Junttila; Laura Sihombing; Maria Sundvall; Jorma A Maatta; V Jukka O Laine; Seppo Yla-Herttuala; Shigeki Higashiyama; Kari Alitalo; Klaus Elenius Journal: FASEB J Date: 2003-09 Impact factor: 5.191
Authors: Steve Zaldua; Frederick C Damen; Rohan Pisharody; Riya Thomas; Kelly D Fan; Giri K Ekkurthi; Sarah B Scheinman; Sami Alahmadi; Felecia M Marottoli; Simon Alford; Kejia Cai; Leon M Tai Journal: Heliyon Date: 2020-05-25