Pin1 Protein Regulates Smad Protein Signaling and Pulmonary Fibrosis

Braun, Ruedi K.; Hu, Jie; Xie, Qifa; Chu, Haiyan; Love, Robert B.; Stodola, Levi; Rosenthal, Louis A.; Szakaly, Renee J.; Sorkness, Ronald L.; Malter, James S.

doi:10.1074/jbc.m111.313684

Cited by 37 publications

(36 citation statements)

References 39 publications

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“…Since Smad6/7 are stable in the nucleus [42,43], we speculate that S1P stimulates transcription of Smad6/7, which is followed by increased nuclear localization of Smad6/7. Although the influence of S1P-induced Smad6/7 upregulation on Runx2 expression and osteoblast differentiation remains unclear, identification of S1P-mediated RhoA/ROCK signaling enhances our understanding of osteoblast differentiation.…”

Section: Discussionmentioning

confidence: 89%

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Sphingosine-1-phosphate/S1PR2-mediated signaling triggers Smad1/5/8 phosphorylation and thereby induces Runx2 expression in osteoblasts

Higashi

Matsuzaki

Hashimoto

et al. 2016

Bone

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Section: Discussionmentioning

confidence: 89%

“…S1P/S1PR2 signaling increases the amount of Smad6/7 protein in the nucleus Smad6 and Smad7 inhibit the BMP signaling pathway [30,31], and Smad6/7 expression levels are generally stable in the nucleus [43,44]. We next examined the effect of S1P on the nuclear expression of Smad6/7.…”

Section: S1p/s1pr2 Signaling Promotes the Nuclear Translocation Of Smad4mentioning

confidence: 99%

Sphingosine-1-phosphate/S1PR2-mediated signaling triggers Smad1/5/8 phosphorylation and thereby induces Runx2 expression in osteoblasts

Higashi

Matsuzaki

Hashimoto

et al. 2016

Bone

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“…Moreover, one study reported that TGF-b1 expression and TGF-b1-mediated fibrosis in human and mouse fibrotic livers occur in a Pin1-dependent manner and are involved in PI3K (phosphatidylinositol 3-kinase)/Akt-or ERK-mediated activator protein-1 (AP-1) phosphorylation. 37 Previous studies have linked Pin1 to the TGF-b1-dependent Smad2/3 activation in lung and liver fibrosis. Regardless of its pleiotropic effect in fibrosis, TGF-b1, and its related signaling elements, also regulates the adaptive growth of cardiomyocytes in response to hypertrophic stress.…”

Section: Indexmentioning

confidence: 99%

Manipulating PML SUMOylation via Silencing UBC9 and RNF4 Regulates Cardiac Fibrosis

et al. 2017

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“…In vitro stimulation of lung fibroblasts. Lung fibroblasts were isolated from GDF-15 ϩ/ϩ , GDF-15 ϩ/Ϫ , and GDF-15 Ϫ/Ϫ littermates as described previously (23). Second-passage cells were seeded in 24-well plates.…”

mentioning

confidence: 99%

Growth Differentiation Factor 15, a Marker of Lung Involvement in Systemic Sclerosis, Is Involved in Fibrosis Development but Is not Indispensable for Fibrosis Development

Lambrecht

Smith

Wilde

et al. 2014

Arthritis & Rheumatology

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ObjectiveTransforming growth factor β superfamily members are involved in the pathogenesis of systemic sclerosis (SSc). Growth differentiation factor 15 (GDF‐15) is a distant member of this family. We undertook this study to evaluate the role of GDF‐15 in SSc pathogenesis.MethodsA longitudinal prospective cohort of SSc patients was screened for serum GDF‐15 levels using enzyme‐linked immunosorbent assay, and associations with clinical data were analyzed. In vitro stimulation experiments were performed on lung fibroblasts. The role of GDF‐15 in fibrosis development in vivo was evaluated in the bleomycin lung fibrosis model in GDF‐15–deficient mice.ResultsGDF‐15 was measured at baseline in serum samples from 119 SSc patients. An increase in GDF‐15 levels was observed in patients classified as having no skin involvement, those with limited cutaneous SSc, and those with diffuse cutaneous SSc. Moreover, baseline serum GDF‐15 levels correlated strongly with disease activity and extent of organ involvement, particularly clinical symptoms of lung fibrosis, including impact on lung function at prospective followup. This was mimicked in the bleomycin model of SSc, in which animals exposed to bleomycin had elevated expression levels of GDF‐15 in lung tissue. Lung fibroblasts isolated from GDF‐15–deficient mice showed reduced induction of interleukin‐6 and CCL2 upon bleomycin stimulation. Surprisingly, no differences in fibrosis development were observed between wild‐type and GDF‐15–deficient animals.ConclusionAn intriguing profile of serum GDF‐15 levels was found in SSc patients. GDF‐15 expression is induced during fibrosis development and markedly correlates with lung function impairment in this disease. The protein may participate in fibrosis initiation, but is not indispensable in the course of fibrosis development in vivo.

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Pin1 Protein Regulates Smad Protein Signaling and Pulmonary Fibrosis

Cited by 37 publications

References 39 publications

Sphingosine-1-phosphate/S1PR2-mediated signaling triggers Smad1/5/8 phosphorylation and thereby induces Runx2 expression in osteoblasts

Sphingosine-1-phosphate/S1PR2-mediated signaling triggers Smad1/5/8 phosphorylation and thereby induces Runx2 expression in osteoblasts

Manipulating PML SUMOylation via Silencing UBC9 and RNF4 Regulates Cardiac Fibrosis

Growth Differentiation Factor 15, a Marker of Lung Involvement in Systemic Sclerosis, Is Involved in Fibrosis Development but Is not Indispensable for Fibrosis Development

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