PPARδ agonist for liver fibrosis in mice

Two peroxisome proliferator-activated receptor delta (PPARδ) agonists KD3010 and GW501516 were evaluated in their role in liver injury and fibrosis. Dr. Schnabla and colleagues in UCSD found that PPARδ agonist KD3010, but not GW501516, dramatically ameliorates liver injury and fibrosis in a carbon tetrachloride (CCl(4)) injection in mice.

Reference:
1: Iwaisako K, Haimerl M, Paik YH, Taura K, Kodama Y, Sirlin C, Yu E, Yu RT, Downes M, Evans RM, Brenner DA, Schnabl B. Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist. Proc Natl Acad Sci U S A. 2012 Apr 25. [Epub ahead of print] PubMed PMID: 22538808.

miR-21 and kidney fibrosis

miR-21 was highly elevated in both animal models and in human transplanted kidneys with nephropathy.

 Deletion of miR-21 in mice resulted in no overt abnormality. However, miR-21 deficient mice showed a decrease in interstitial fibrosis in response to kidney injury.

The study found that peroxisome proliferator–activated receptor α (PPARα), a regulator of lipid metabolism, is a direct target of miR-21. Overexpression of PPARα in the kidney during injury inhibited fibrosis in mice; conversely, in mice that lacked PPARα, inhibition of miR-21 no longer protected against kidney fibrosis. 

The study suggested that anti-miR to miR-21 may be beneficial to the patients  with kidney fibrosis.

References:
Chau BN, Xin C, Hartner J, Ren S, Castano AP, Linn G, Li J, Tran PT, Kaimal V, Huang X, Chang AN, Li S, Kalra A, Grafals M, Portilla D, MacKenna DA, Orkin SH, Duffield JS. MicroRNA-21 promotes fibrosis of the kidney by silencing metabolic pathways. Sci Transl Med. 2012 Feb 15;4(121):121ra18. PubMed PMID: 22344686.

http://stm.sciencemag.org

Lecithinized superoxide dismutase for IPF

Epithelial cell injury was believed a leading process to lung fibrosis. The injury includes reactive oxygen species (ROS), such as superoxide anion. Superoxide dismutase (SOD) catalyses the dismutation of superoxide anion to hydrogen peroxide. The rationale would be that an increase of SOD may reduce ROS, leading to less injury.

A team of Japanese scientists tested if inhalation of PC-SOD, compared with oral administration of pirfenidone, affects bleomycin-induced pulmonary fibrosis in a bleomycin-induced lung fibrosis model in mice. The authors concluded that PC-SOD suppressed the bleomycin-induced pulmonary inflammatory response and production of superoxide anions in the lung more effectively than pirfenidone.

Reference:
Tanaka KI, Azuma A, Miyazaki Y, Sato K, Mizushima T. Effects of lecithinized superoxide dismutase and/or pirfenidone against bleomycin-induced pulmonary fibrosis. Chest. 2012 Mar 29. [Epub ahead of print] PubMed PMID: 22459774.