EMAIL THIS PAGE TO A FRIEND

Molecular therapy : the journal of the American Society of Gene Therapy

Angiopoietin-like 4 stimulates STAT3-mediated iNOS expression and enhances angiogenesis to accelerate wound healing in diabetic mice.


PMID 24903577

Abstract

Impaired wound healing is a major source of morbidity in diabetic patients. Poor outcome has, in part, been related to increased inflammation, poor angiogenesis, and deficiencies in extracellular matrix components. Despite the enormous impact of these chronic wounds, effective therapies are lacking. Here, we showed that the topical application of recombinant matricellular protein angiopoietin-like 4 (ANGPTL4) accelerated wound reepithelialization in diabetic mice, in part, by improving angiogenesis. ANGPTL4 expression is markedly elevated upon normal wound injury. In contrast, ANGPTL4 expression remains low throughout the healing period in diabetic wounds. Exogenous ANGPTL4 modulated several regulatory networks involved in cell migration, angiogenesis, and inflammation, as evidenced by an altered gene expression signature. ANGPTL4 influenced the expression profile of endothelial-specific CD31 in diabetic wounds, returning its profile to that observed in wild-type wounds. We showed ANGPTL4-induced nitric oxide production through an integrin/JAK/STAT3-mediated upregulation of inducible nitric oxide synthase (iNOS) expression in wound epithelia, thus revealing a hitherto unknown mechanism by which ANGPTL4 regulated angiogenesis via keratinocyte-to-endothelial-cell communication. These data show that the replacement of ANGPTL4 may be an effective adjunctive or new therapeutic avenue for treating poor healing wounds. The present finding also confirms that therapeutic angiogenesis remains an attractive treatment modality for diabetic wound healing.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

D8001
3,3′-Diaminobenzidine, ≥99% (HPLC)
C12H14N4
D12384
3,3′-Diaminobenzidine, 99%
C12H14N4
B3773 Anti-Human IgG (Fc specific)−Biotin antibody, Mouse monoclonal, clone HP-6017, purified from hybridoma cell culture
EHU122051 MISSION® esiRNA, esiRNA human STAT3 (esiRNA1)
EMU082481 MISSION® esiRNA, esiRNA targeting mouse Stat3 (esiRNA1)
G2904 Monoclonal Anti-Goat/Sheep IgG antibody produced in mouse, clone GT-34, ascites fluid
A8062 Monoclonal Anti-Goat/Sheep IgG–Alkaline Phosphatase antibody produced in mouse, clone GT-34, purified immunoglobulin, buffered aqueous glycerol solution
B3148 Monoclonal Anti-Goat/Sheep IgG–Biotin antibody produced in mouse, clone GT-34, purified immunoglobulin, buffered aqueous solution
F4891 Monoclonal Anti-Goat/Sheep IgG−FITC antibody produced in mouse, clone GT-34, purified immunoglobulin, buffered aqueous solution
I6135 Monoclonal Anti-Human IgG (Fab specific) antibody produced in mouse, clone GG-6, ascites fluid
I6260 Monoclonal Anti-Human IgG (Fc specific) antibody produced in mouse, clone GG-7, ascites fluid
I6760 Monoclonal Anti-Human IgG (Fc specific) antibody produced in mouse, clone HP-6017, ascites fluid
F5016 Monoclonal Anti-Human IgG (Fc specific)−FITC antibody produced in mouse, clone HP-6017, purified immunoglobulin, buffered aqueous solution
I5885 Monoclonal Anti-Human IgG (γ-chain specific) antibody produced in mouse, clone GG-5, ascites fluid
I9513 Monoclonal Anti-Human IgG2 (Fc specific) antibody produced in mouse, clone HP-6002, ascites fluid
I9888 Monoclonal Anti-Human IgG4 (pFc′ specific) antibody produced in mouse, clone HP-6023, ascites fluid
R0761 Monoclonal Anti-Rat IgG2a antibody produced in mouse, clone R2A-2, ascites fluid