CD36 is a novel and potential anti-fibrogenic target in albumin-induced renal proximal tubule fibrosis.
Albumin is not only a risk factor for diabetic nephropathy (DN), but also a therapeutic target. Hence, scientists have long sought ways to elucidate the interactions between albumin and diabetic renal tubule fibrosis. CD36, a surface receptor for thrombospondin-1, has been reported to interact with latent transforming growth factor-beta1 (TGF-beta1) and activate its fibrogenic bioactivity. This study elucidates the interactions between CD36 and renal tubule fibrosis. LLC-PK1 cells were applied to represent renal proximal tubule cells. The expression of CD36 was evaluated by flow cytometry. Fibronectin was assayed by Western blot and enzyme-linked immunosorbent assay (ELISA). Bioactive TGF-beta1 was assayed by ELISA. We demonstrated that albumin was shown significantly to inhibit cell growth without affecting hypertrophy status since protein content and cell size remained unaffected under albumin treatment. Moreover, albumin dose-dependently (0, 1, or 10 mg/ml) enhanced the secretion of bioactive TGF-beta1 and fibronectin with the upregulation of CD36. Intriguingly, CD36 siRNA, a potent silencer for CD36 effectively suppressed the albumin-induced increase in CD36, TGF-beta1, and even fibronectin level. Accordingly, albumin is a pro-fibrogenic factor for proximal tubule cells since albumin per se markedly upregulated the expression of TGF-beta1 and fibronectin. Most importantly, CD36 may mediate albumin-induced cellular fibrosis since CD36 siRNA appeared to have anti-fibrosis effects. This work suggests that CD36 is a novel and potential therapeutic target for diabetic renal tubule fibrosis.
Yang
Yu-Lin
YL
Department of Biological Science and Technology, Chung Hwa University of Medical Technology, Tainan, Taiwan. tel0955443221@gmail.com
Lin
Shyh-Horng
SH
Chuang
Lea-Yea
LY
Guh
Jinn-Yuh
JY
Liao
Tung-Nan
TN
Lee
Tao-Chen
TC
Chang
Wen-Teng
WT
Chang
Fang-Rong
FR
Hung
Min-Yuan
MY
Chiang
Tai-An
TA
Hung
Chien-Ya
CY
D000418:Albumins / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D006984:Hypertrophy; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D034741:RNA, Small Interfering / Q000235:genetics; D013552:Swine; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000418:Albumins; D018955:CD36 Antigens; D005353:Fibronectins; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1