Effect of Regulating the Expression of HSP47 on Collagen Metabolism in Scleral Fibroblasts

Guo, Qingge; Tian, Qingshan; Tian, Xiang; Liu, Taixiang

doi:10.1080/02713683.2020.1805471

Cited by 6 publications

(8 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have indicated a correlation between HSP47 levels in the ER and both intracellular and extracellular levels of type I collagen assembly in smooth muscle cells (SMCs) [ 43 ]. Furthermore, the upregulation of HSP47 has been shown to increase mRNA expression levels of collagen types I, III, and V in scleral fibroblasts [ 44 ]. Consequently, our discovery that HSP47 induces the expression of type I collagen in fibroblasts aligns with and reinforces these prior findings.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin

Ham,

Pyo,

Kang

et al. 2024

Cells

View full text Add to dashboard Cite

Heat shock protein 47 (HSP47), also known as SERPINH1, functions as a collagen-specific molecular chaperone protein essential for the formation and stabilization of the collagen triple helix. Here, we delved into the regulatory pathways governed by HSP47, shedding light on collagen homeostasis. Our investigation revealed a significant reduction in HSP47 mRNA levels in the skin tissue of older mice as compared to their younger counterparts. The augmented expression of HSP47 employing lentivirus infection in fibroblasts resulted in an increased secretion of type I collagen. Intriguingly, the elevated expression of HSP47 in fibroblasts correlated with increased protein and mRNA levels of type I collagen. The exposure of fibroblasts to IRE1α RNase inhibitors resulted in the reduced manifestation of HSP47-induced type I collagen secretion and expression. Notably, HSP47-overexpressing fibroblasts exhibited increased XBP1 mRNA splicing. The overexpression of HSP47 or spliced XBP1 facilitated the nuclear translocation of β-catenin and transactivated a reporter harboring TCF binding sites on the promoter. Furthermore, the overexpression of HSP47 or spliced XBP1 or the augmentation of nuclear β-catenin through Wnt3a induced the expression of type I collagen. Our findings substantiate that HSP47 enhances type I collagen expression and secretion in fibroblasts by orchestrating a mechanism that involves an increase in nuclear β-catenin through IRE1α activation and XBP1 splicing. This study therefore presents potential avenues for an anti-skin-aging strategy targeting HSP47-mediated processes.

show abstract

Section: Discussionmentioning

confidence: 99%

“…While some studies have suggested the potential for HSP47 to upregulate collagen expression [ 44 ], the specific signaling pathways responsible for this effect remain unclear. Thus, we sought to elucidate the regulatory mechanisms through which HSP47 influences type I collagen expression.…”

Section: Discussionmentioning

confidence: 99%

HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin

Ham,

Pyo,

Kang

et al. 2024

Cells

View full text Add to dashboard Cite

show abstract

“…Approaches that slow or stop the synthesis and deposition of collagen may hold promise as an anti-fibrotic therapy. Recent data suggests that increased HSP47 is closely related to the immoderate deposition of collagen in several fibrotic diseases [8][9][10][11][12][13][14] . Our research revealed that up-regulated HSP47 correlates with the elevated expression of collagen I and III within the conjunctival blebs after trabeculectomy [17] .…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we picked this time to investigate our adenovirus construct's silencing effect. Guo et al [12] revealed that decreased expression of HSP 47 gave rise to down-regulated expression levels of collagen in scleral fibroblasts. Wang et al [23] found that antisense treatment against the HSP47 gene suppressed the accumulation of collagen I during wound healing of neonatal rat skin, and assumed that silencing of the HSP47 gene had a therapeutic potential to inhibit skin scarification.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is of significant clinical importance to target a novel molecule that could play a vital role during postoperative wound healing in order to minimize GFS failure. Heat shock protein (HSP47), a collagen-specific molecular chaperon, is closely related to fibrotic and ocular fibrosis diseases [8][9][10][11][12][13][14] . Recent studies have shown that excessive collagen accumulation is a key pathological process of bleb scarring [15][16] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model

Wang,

Yan

2023

Int J Ophthalmol

View full text Add to dashboard Cite

AIM: To evaluate the effectiveness of knock-down of heat shock protein 47 (HSP47) on conjunctival bleb scarring in a rat model and its possible mechanism. METHODS: Male Sprague–Dawley rats were used for glaucoma filtration surgery (GFS) and were treated with either phosphate buffered solution, shControl, mitomycin C, or sh-HSP47 using a microsyringe immediately after GFS. The morphology of filtering blebs was observed postoperatively. The levels of HSP47 were analyzed at 2, 5, 8, and 11d after GFS via real time quantitative polymerase chain reaction (PCR) and Western blot. The silencing effect of HSP47, the expression of collagen I and III, and the potential signaling pathways of HSP47 during scarification were explored 11d post GFS. The protein levels of transforming growth factor-β1 (TGF-β1), phospho-Smad2 (pSmad2), phospho-Smad3 (p-Smad3), and phospho-p38 (p-p38) were also analyzed using Western blot. RESULTS: Sh-HSP47 treatment significantly prolonged the functional filtration bleb retention. The levels of HSP47 were increased significantly at 5, 8, and 11d postoperatively compared to the control group (P<0.05, P<0.01, and P<0.001). The levels of HSP47 protein at day 11 postoperatively were significantly down-regulated after HSP47 silencing using sh-HSP47 adenovirus transfection (P<0.01). Expression levels of collagen I and III within the blebs were significantly reduced in the absence of HSP47 (P<0.01). Moreover, the protein levels of TGF-β1, p-Smad2/3, and p-p38 were dramatically inhibited after treatment with sh-HSP47 (P<0.01). CONCLUSION: The inhibitory effects of HSP47 knock-down on scarring after GFS have the potential to be an efficacious therapeutic option for the treatment of conjunctival bleb scarring.

show abstract

MicroRNA-29a inhibits collagen expression and induces apoptosis in human fetal scleral fibroblasts by targeting the Hsp47/Smad3 signaling pathway

Tang

Liu

et al. 2022

Experimental Eye Research

View full text Add to dashboard Cite

Effect of Regulating the Expression of HSP47 on Collagen Metabolism in Scleral Fibroblasts

Cited by 6 publications

References 21 publications

HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin

HSP47 Increases the Expression of Type I Collagen in Fibroblasts through IRE1α Activation, XBP1 Splicing, and Nuclear Translocation of β-Catenin

Effectiveness of conjunctival bleb scarring by knock-down of heat shock protein 47 in rat model

MicroRNA-29a inhibits collagen expression and induces apoptosis in human fetal scleral fibroblasts by targeting the Hsp47/Smad3 signaling pathway

Contact Info

Product

Resources

About