Cho S, Roh K, Park J, Park YS, Lee M, Cho S, Kil EJ, Cho MJ, Oh JS, Byun HS, Cho SH, Park K, Kang H, Koo J, Yeom CH, Lee S, et al.
Scientific reports. Date of publication 2017 Feb 24;volume 7(1):35.
1. Sci Rep. 2017 Feb 24;7(1):35. doi: 10.1038/s41598-017-00085-z.
Hydrolysis of Hyaluronic Acid in Lymphedematous Tissue Alleviates Fibrogenesis
via TH1 Cell-Mediated Cytokine Expression.
Cho S(1), Roh K(1), Park J(1), Park YS(1), Lee M(1), Cho S(1), Kil EJ(1), Cho
MJ(1), Oh JS(1), Byun HS(1), Cho SH(1), Park K(2), Kang H(3), Koo J(4), Yeom
CH(5), Lee S(6).
Author information:
(1)Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419,
Republic of Korea.
(2)Department of Food Science and Biotechnology, Sungkyunkwan University, Suwon,
16419, Republic of Korea.
(3)Department of Oriental Medical Science, Graduate School of East-West Medical
Science, Kyunghee University, Yongin, 17104, Republic of Korea.
(4)Natural Products Research Department, Gyeonggi Institute of Science &
Technology, Suwon, 16229, Republic of Korea.
(5)U-Cell Clinic, Seoul, 06605, Republic of Korea.
(6)Department of Genetic Engineering, Sungkyunkwan University, Suwon, 16419,
Republic of Korea. cell4u@skku.edu.
Although surgery and radiation are beneficial for treating cancer, they can also
lead to malfunctions of the lymphatic system such as secondary lymphedema. This
abnormality of the lymphatic system is characterized by severe swelling,
adipogenesis, inflammation, and fibrosis in the lymphedematous region. Moreover,
the proliferation of fibrotic tissue in the lymphedematous region generates edema
that is no longer spontaneously reversible. No treatment for fibrosis has been
validated in patients with lymphedema. In our efforts to develop a therapeutic
agent for lymphedema fibrosis, we used a newly established mouse hind limb model.
Previous studies have demonstrated that hyaluronic acid accumulates in the
lymphedematous region. Thus, we challenged mice with of hyaluronidase (HYAL),
with the aim of reducing fibrogenesis. After subcutaneous injections in the
lymphedematous mouse leg every two days, the volume of lymphedema had reduced
significantly by 7 days post-operation. Histochemical analysis indicated that
collagen accumulation and myofibroblast differentiation were decreased in
epidermal tissues after HYAL injection. Moreover, it was associated with
upregulation of interferon-gamma, increased numbers of Th1 cells, and
downregulation of interleukin-4 and interleukin-6 in the lymphedematous region
and spleen. These results indicate that hydrolysis of hyaluronic acid can boost
an anti-fibrotic immune response in the mouse lymphedema model.
DOI: 10.1038/s41598-017-00085-z
PMCID: PMC5428353
PMID: 28232732 [Indexed for MEDLINE]
