ジャーナルクラブ Am J Physiol Lung Cell Mol Physiol 2012年12月号 Sonic Hedgehogシグナル

特発性肺線維症におけるSonic Hedgehogシグナルの関与


Role of Sonic Hedgehog in idiopathic pulmonary fibrosis.
Bolaños AL, Milla CM, Lira JC, Ramírez R, Checa M, Barrera L, García-Alvarez J, Carbajal V, Becerril C, Gaxiola M, Pardo A, Selman M.
Am J Physiol Lung Cell Mol Physiol. 2012 Dec;303(11):L978-90.

The Hedgehog System Machinery Controls Transforming Growth Factor-β-Dependent Myofibroblastic Differentiation in Humans: Involvement in Idiopathic Pulmonary Fibrosis.
Cigna N, Farrokhi Moshai E, Brayer S, Marchal-Somme J, Wémeau-Stervinou L, Fabre A, Mal H, Lesèche G, Dehoux M, Soler P, Crestani B, Mailleux AA.
Am J Pathol. 2012 Dec;181(6):2126-37.

MicroRNAs in idiopathic pulmonary fibrosis.
Pandit KV, Milosevic J, Kaminski N.
Transl Res. 2011 Apr;157(4):191-9. doi: 10.1016/j.trsl.2011.01.012. Epub 2011 Feb 4. Review.


参考　RT-PCR
　　　Forward 　　　　　　　　　　　　　Reverse
SHH 5′-GAAAGCAGAGAACTCGGTGG-3′ 5′-CTCAGGTCCTTCACCAGCTT-3′
IHH 5′-TCAGCCTGCTCTCACTACGA-3′ 5′-CAAAGGGGCCTAAGATGGAT-3′
DHH 5′-GACCGCAACAAGTATGGGTT-3′ 5′-TATCAGCTTTGACCGACACG-3′
PTC 5′-TGGCATAGGAGTGGAGTTCA-3′ 5′-ATCAGCACTCCCAGCAGAGT-3′
HHIP 5′-CATGTCGTCATGGAGGTGTC-3′ 5′-GCGGATGTTTCTGTCCACTT-3′
SMO 5′-CAGCAAGATCAACGAGACCA-3′ 5′-GGCAGCTGAAGGTAATGAGC-3′
GLI1 5′-CCAGCCAGAGAGACCAACA-3′ 5′-ATCCGACAGAGGTGAGATGG-3′
GLI2 5′-TTTATGGGCATCCTCTCTGG-3′ 5′-AAGGCTGGAAAGCACTGTGT-3′
GLI3 5′-CCTCCCAACTCCTCACACAT-3′ 5′-CAACACCAACTGGTCCCTCT-3′
SUFU 5′-ACATGCTGCTGACAGAGGAC-3′ 5′-CAGACACCAACGATCTGGAG-3′
SPOP 5′-TTCTGCGAGGTGAGTGTTGT-3′ 5′-GGCACTCAGGAACCTTTACC-3′
UBC 5′-CACTTGGTCCTGCGCTTGA-3′ 5′-TTTTTTGGGAATGCAACAACTT-3′
αSMA 5′-GAAGAGCATCCCACCCTGC-3′ 5′-ATTTTCTCCCGGTTGGCCT-3′
FN1 5′-GCCAACAGGATGACATGAAT-3′ 5′-CATACCCGCCGAATGTAGGA-3′
α2COL-1 5′-TTGAGACTCAGCCACCCAGAGT-3′ 5′-CAGTTCTTGGCTGGGATGTTTT-3′


Hedgehog pathwayのIPF関連分子mRNA levelの修飾作用
Immunostaining　Positive regulators
SHH ↓ Positive in fibrotic lesions; ↓ in “normal” areas
IHH ↓ ND
DHH = ND
SMO = =
GLI1 = Nuclear in fibrotic lesions
GLI2 = Nuclear in fibrotic lesions and in “normal” areas
SUFU ↓ Nuclear in fibrotic lesions
Negative regulators
PTC ↓ ↓ in fibrotic lesions
HHIP ↓ ND
GLI3 = ↓ in fibrotic lesions
SPOP ↓ ND

↓, decreased compared with control lung tissue; =, unchanged; ND, not determined.