Disease relevance of SERPINH1

• The surface-exposed RA-A47 may induce autoantibodies and inflammatory reactions in autoimmune disease situations such as rheumatoid arthritis [1].
• Two animals (a Mandrillus sphinx and a Cercocebus agilis) exhibited a complete HTLV-1 seroreactivity pattern while two others lacked either the p24 (a Mandrillus sphinx) or the MTA-1/gp46 bands (a Pan troglodytes) [2].
• These studies showed that colligin/Hsp47 was not limited to any phase of the cell cycle in epidermoid carcinoma cells [3].
• Expression profiles of collagens, HSP47, TGF-beta1, MMPs and TIMPs in epidermolysis bullosa acquisita [4].
• Hsp47 is a heat stress protein that interacts with procollagen in the lumen of the endoplasmic reticulum, which is vital for collagen elaboration and embryonic viability [5].
• We propose that Hsp47 may therefore play a role in hemostasis and thrombosis [6].

High impact information on SERPINH1

• Saccharomyces cerevisiae mutants lacking the CBP1 homolog RCN1 are, like calcineurin mutants, sensitive to lithium cation stress [7].
• The 4-hydroxyproline-containing procollagen polypeptide chains were of full length and formed molecules with stable triple helices even though Pichia probably has no Hsp47-like protein [8].
• Anchorage-dependent cell lines like L6 myoblasts and normal rat kidney fibroblasts produced both colligin and procollagen I mRNA, but the level of both was concurrently reduced considerably in their ras-transformed counterparts [9].
• Similarly, during the differentiation of L6 myoblasts, levels of both colligin and procollagen declined together [9].
• Parallel regulation of procollagen I and colligin, a collagen-binding protein and a member of the serine protease inhibitor family [9].

Chemical compound and disease context of SERPINH1

• The abundance of HSP47 protein was unchanged by treatment of cultured human HSC with TGF-beta1, angiotensin II, hypoxia and a number of other treatments intended to increase collagen synthesis [10].
• This study therefore indicates that the C-terminal half of gp46, especially the amino acid sequence from 200 to 308, contains the most reactive epitopes of the HTLV-1 gp61 envelope glycoprotein [11].
• In the present study, we examined the effect of HSP47 antisense oligonucleotides (ODNs) on the development of experimental peritoneal fibrosis induced by daily intraperitoneal injections of chlorhexidine gluconate (CG) [12].
• Formalin-fixed, paraffin-embedded lung sections from 17 autopsies of patients with various pulmonary fibrotic diseases, e.g., organizing pneumonia, interstitial pneumonia, idiopathic pulmonary fibrosis, and diffuse alveolar damage, were stained with monoclonal antibodies for alpha-smooth muscle actin, vimentin, CD68, Type III collagen, and HSP47 [13].
• Undifferentiated F9 embryonal carcinoma cells lacked gp46 but the glycoprotein was induced when the cells were made to differentiate in the presence of retinoic acid [14].

Biological context of SERPINH1

• Induction of HSP47 by TGF-beta has been previously reported in rat skeletal myoblasts and mouse osteoblasts, but not in human diploid fibroblasts [15].
• Associated with this phenomenon, RA-A47 appeared on the cell surface concomitant with upregulation of metabolic factors related to cartilage destruction [1].
• Here, we show that the enhanced surface expression of RA-A47 on a chondrocytic cell line, HCS-2/8 was also a direct result of RA-A47 downregulation by ra-a47 anti-sense oligonucleotide, independent of the cytokine effects [1].
• Previously, we showed that gene expression of the rheumatoid arthritis-related antigen RA-A47, which is identical to human heat shock protein (HSP)47, was downregulated in chondrocytes by inflammatory cytokines such as TNFalpha [1].
• The human genome has only one functional hsp47 gene (CBP2) and a pseudogene (pshsp47) [16].

Anatomical context of SERPINH1

• Boyden chamber tumor invasion assays and colloidal gold migration assays utilizing a reconstituted basement membrane (Matrigel), collagen type I, and laminin-5 substrates revealed that cell lines expressing constitutive high levels of colligin/Hsp47 manifested the lowest invasion and migration indices [3].
• These data indicate that colligin/Hsp47 is anchored to the cell membrane in a complex with CD9 where it moderates tumor cell invasion and motility possibly by acting as a serpin protein inhibitor or as a receptor for collagen [3].
• Together, these findings indicate a novel means by which type I collagen production is regulated by the endoplasmic reticulum constituent, Hsp47, and suggest a potential basis for inherent differences in collagen production within the population [5].
• To evaluate the effects of Hsp47 on collagen production we infected human vascular smooth muscle cells (SMCs) with a retrovirus containing Hsp47 cDNA [5].
• To show that the isolated cDNA encodes RA-A47 protein, it was expressed in Cos-7 cells [17].

Associations of SERPINH1 with chemical compounds

• The CD9 was colocalized with RA-A47 on the cell surface, where it may have affected integrin signaling [1].
• The effects of Hsp47 were qualitatively distinct from, and independent of, those of ascorbate and the combination of both factors yielded an even more intricate fibril network [5].
• Colligin, a collagen-binding glycoprotein localized to endoplasmic reticulum, belongs to the serpin superfamily [18].
• METHODS: The effects of NO which was generated by two types of NO donors, sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP), on type I collagen and HSP47 and their related mRNA expression were examined with ELISA and RT-PCR [19].
• Treatment of SCC cells with CBP2/Hsp47 antisense phosphorothioate oligonucleotides modulated the production of collagen XVIII but not its expression [20].

Physical interactions of SERPINH1

• Both PDI and the collagen-binding protein hsp47 showed a similar pH-dependent interaction with folded collagen, dissociating when the pH was lowered to pH 6 [21].

Regulatory relationships of SERPINH1

• TGF-beta1 induced the expression of HSP47 and type I collagen by conjunctival fibroblasts [22].
• Moreover, parallel regulation of proalpha1(I)collagen and Hsp47 mRNA expression occurred with cultured human smooth muscle cells stimulated with transforming growth factor-beta1 or fibroblast growth factor-2 [23].

Other interactions of SERPINH1

• The enhancement of HSP47 synthesis and their trimer formation of HSF1 were augmented by using a combination of both cytokines [15].
• Isolation and characterization of a rheumatoid arthritis-specific antigen (RA-A47) from a human chondrocytic cell line (HCS-2/8) [24].
• Immunoprecipitation studies following protein crosslinking revealed that Hsp47 was associated with a number of membrane proteins including the tetraspanin CD9 [3].
• These findings suggest colligin may function as a collagen-specific molecular chaperon and play a role in the process of retinoic acid-induced differentiation [25].
• Dual fluorescence confocal microscopy showed colocalization of HSP47 with synaptophysin, a marker for HSC [10].

Analytical, diagnostic and therapeutic context of SERPINH1

• Compared to the controls, an increased expression of type I collagen, type III collagen and HSP47 was detected in conjunctival biopsy sections of patient with EBA using immunohistochemistry [4].
• In animal models of liver injury, hepatic stellate cells (HSC) have been identified as a source of HSP47 [10].
• When dermal fibroblasts were treated with various concentrations of TGF-beta 1 (6.25, 12.5, 25, 50 and 100 ng/ml for 24 h), it induced the expression of both type I collagen and HSP47, as determined by quantitative real-time PCR [26].
• The goal of the present study was to examine the possible involvement of two important wound-healing-associated proteins-heat shock protein 47 (Hsp47), fibronectin (Fn), and its oncofetal isoforms-in DD, using clinical tissue samples and primary cell cultures [27].
• The level of HSP 47 and/or procollagen expression in fibroblasts was measured by real-time RT-PCR (mRNA transcripts) and by flow cytometry (immunochemistry technique for measurement of arbitrary fluorescence intensity) [28].

References