Premium
Gastric Sonic Hedgehog Acts as a Chemoattractant for Macrophages During Tissue Regeneration
Author(s) -
Engevik Amy Christine,
Martin Jason R.,
Tritschler Julie A.,
Feng Rui,
Schumacher Michael A.,
Yang Li,
Zavros Yana
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.944.6
Subject(s) - sonic hedgehog , regeneration (biology) , hedgehog , smoothened , wound healing , immune system , microbiology and biotechnology , chemotaxis , biology , inflammation , cancer research , receptor , immunology , biochemistry , signal transduction
Sonic Hedgehog (Shh) has been shown to regulate wound healing in various tissues. Immune cells such as macrophages (Mø) are also known to regulate repair. Despite its known function in tissue regeneration the role of Shh as a regulator of the immune system during gastric tissue repair remains unknown. Hypothesis Shh secreted from the gastric epithelium mediates the recruitment of Møs that drives tissue repair. A mouse model expressing a parietal cell‐specific deletion of Shh (PC‐Shh KO ) and a mouse model expressing a myeloid cell‐specific deletion of Hedgehog receptor Smoothened (LysMCre/Smo KO ) were used. Acetic acid ulcers were induced and samples collected. In controls, ulcers healed within 7 days. Tissue regeneration was accompanied by the recruitment of Møs to the stomach within 48 hours post injury. Control mice had elevated expression of cytokines and the pro‐angiogenic factor VEGF that correlated with an increased Shh tissue concentration within 3 days post injury. PC‐Shh KO mice showed complete loss of ulcer repair, the absence of Mø recruitment and reduced Shh tissue concentrations. LysMCre/Smo KO mice exhibited delayed repair of ulcerated tissue. While in vitro Møs migrated towards the Shh gradient, cells isolated from LysMCre/Smo KO mice failed to respond. Gastric Shh facilitates tissue repair by acting as a Mø chemoattractant. Funding: ACS Research Scholar Award 119072‐RSG‐10–167‐01‐MPC (Y. Zavros)