Effect of SOST gene deletion on the progression of renal interstitial fibrosis in obstructive kidney injury.
OBJECTIVE
The role of SOST/sclerostin in mediating tissue fibrogenic response to injury/inflammation remains largely unknown. Thus, we conducted this study to determine whether SOST/sclerostin plays a role in renal interstitial fibrosis (RIF) for the first time.


METHODS
Unilateral ureteral obstruction (UUO) was performed to create obstructive kidney injury model. Twelvemale SOST knockout (SOST KO) mice and 12 age-matched wild-type (WT) mice were divided into three groups: sham surgery, UUO 3 d and UUO 7 d. The mice were sacrificed at each time point and kidney tissues were collected. Histopathological changes were evaluated by hematoxylin and eosin and Masson staining, while α-smooth muscle actin (α-SMA), type I collagen (Col-I) and fibronectin (FN) expression levels were detected by RT-PCR and western-blot.


RESULTS
In sham control group, neither WT nor SOST KO exhibited fibrotic change. On 3 days after UUO, total renal histopathological score and fibrotic area were aggravated and α-SMA, Col-I and FN expressions were upregulated, but no difference was observed between WT and SOST KO. On 7 days after UUO, compared with WT, SOST KO mice showed higher total renal histopathological score and fibrotic area percentage, as well as a higher level of fibrogenic marker mRNA/protein expression (except for α-SMA mRNA and FN mRNA).


CONCLUSIONS
It is supposed that SOST gene is involved in the regulation of RIF progression. In obstructive kidney injury, SOST gene deletion would probably enhance renal fibrogenic response and promote the progression of RIF. But more evidences are needed to further identify the role of SOST/sclerostin in mediating RIF progression.
a Department of Orthodontics , State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu , China .
Lu-Fei
LF
Wang
b Oral Department , Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital , Chengdu , China , and.
Hao
H
Wu
a Department of Orthodontics , State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu , China .
Yang
Y
Xu
c Oral Biology Program, School of Dentistry, University of North Carolina at Chapel Hill , Chapel Hill , NC , USA.
Meng
M
Deng
a Department of Orthodontics , State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu , China .
Xiang-Long
XL
Han
a Department of Orthodontics , State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University , Chengdu , China .
Ding
D
Bai
D000199:Actins / Q000378:metabolism; D058186:Acute Kidney Injury / Q000150:complications*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism; D004195:Disease Models, Animal; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D006023:Glycoproteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D014517:Ureteral Obstruction / Q000150:complications*
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D024042:Collagen Type I; D005353:Fibronectins; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C486030:Sost protein, mouse; C544013:alpha-smooth muscle actin, mouse
LRP-6; SOST gene; renal interstitial fibrosis; sclerostin; unilateral ureteral obstruction