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2015 ; 6
(ä): 82
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TGF-?/Smad signaling in renal fibrosis
#MMPMID25852569
Meng XM
; Tang PM
; Li J
; Lan HY
Front Physiol
2015[]; 6
(ä): 82
PMID25852569
show ga
TGF-? (transforming growth factor-?) is well identified as a central mediator in
renal fibrosis. TGF-? initiates canonical and non-canonical pathways to exert
multiple biological effects. Among them, Smad signaling is recognized as a major
pathway of TGF-? signaling in progressive renal fibrosis. During fibrogenesis,
Smad3 is highly activated, which is associated with the down-regulation of an
inhibitory Smad7 via an ubiquitin E3-ligases-dependent degradation mechanism. The
equilibrium shift between Smad3 and Smad7 leads to accumulation and activation of
myofibroblasts, overproduction of ECM (extracellular matrix), and reduction in
ECM degradation in the diseased kidney. Therefore, overexpression of Smad7 has
been shown to be a therapeutic agent for renal fibrosis in various models of
kidney diseases. In contrast, another downstream effecter of TGF-?/Smad signaling
pathway, Smad2, exerts its renal protective role by counter-regulating the Smad3.
Furthermore, recent studies demonstrated that Smad3 mediates renal fibrosis by
down-regulating miR-29 and miR-200 but up-regulating miR-21 and miR-192. Thus,
overexpression of miR-29 and miR-200 or down-regulation of miR-21 and miR-192 is
capable of attenuating Smad3-mediated renal fibrosis in various mouse models of
chronic kidney diseases (CKD). Taken together, TGF-?/Smad signaling plays an
important role in renal fibrosis. Targeting TGF-?/Smad3 signaling may represent a
specific and effective therapy for CKD associated with renal fibrosis.
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