Both mesenteric adipose tissue (MAT) and lymphatic vessels (LVs) play important roles in the pathogenesis of
Crohn's disease (CD), and
adipokines have been implicated in the crosstalk between MAT and LVs.
Apelin, a newly identified
adipokine, has been demonstrated to be crucial in the development and stabilization of LVs. We aimed to identify the expression of
apelin in MAT of CD patients and explore whether
apelin influences the disease course in murine
colitis and determine its contributions to LVs. Expression of
apelin in MAT specimens from patients with CD (n = 24) and without CD (control, n = 12) was detected.
Il-10 deficient (Il-10-/-) mice with established
colitis were administered
apelin, and untreated and wild-type mice served as controls (n = 8 for each group). Disease activity and colonic
inflammation was evaluated. The LV density, lymphatic drainage function and related signaling pathways were also analyzed. We found that MAT from CD patients expressed a higher level of
apelin compared with that from controls. Systemic delivery of
apelin significantly ameliorated chronic
colitis in Il-10-/- mice, demonstrated by decreased disease activity index and inflammatory scores, and lower levels of Tnf-α, Il-1β and
Il-6. Increased LV density and podoplanin levels indicated that
apelin promoted lymphangiogenesis.
Evans blue dye and fluorescent lymphangiography revealed an enhanced lymphatic drainage function in
apelin-treated mice. The role of
apelin was found to be related to the activation of the Akt and Erk signaling pathways. These results indicate that the
adipokine apelin was highly expressed in MAT of CD patients and has a promising role in ameliorating experimental
colitis by promoting intestinal lymphatic functions, suggesting the potential crosstalk between
adipokines and LVs in MAT in CD status.
Therapies with
adipokines, such as
apelin, may be a novel approach for the treatment of CD.