Role Of Collagen Type Research Articles

The role of collagen type I/III ratio in the etiology of sacrococcygeal pilonidal

The role of collagen type I/III ratio in the etiology of sacrococcygeal pilonidal

Metformin Attenuates Hyperglycaemia-Stimulated Pro-Fibrotic Gene Expression in Adventitial Fibroblasts via Inhibition of Discoidin Domain Receptor 2.

Molecular mechanisms underlying the diverse therapeutic effects of anti-diabetic metformin, beyond its anti-hyperglycaemic effects, remain largely unclear. Metformin is reported to reduce the long-term complications of diabetes, including cardiovascular fibrosis and remodelling. Our recent investigations show that Discoidin Domain Receptor 2 (DDR2), a Collagen receptor tyrosine kinase, has an obligate regulatory role in Collagen type I gene expression in cardiac and vascular adventitial fibroblasts, and that it may be a molecular link between arterial fibrosis and metabolic syndrome in rhesus monkeys. Using gene knockdown and overexpression approaches, the present study examined whether DDR2 is a target of metformin and whether, by targeting DDR2, it inhibits Fibronectin and Collagen type I expression in rat aortic adventitial fibroblasts exposed to hyperglycaemic conditions. Metformin was found to attenuate hyperglycaemia-induced increase in DDR2 mRNA and protein expression by inhibiting TGF-β1/SMAD2/3 signalling that mediates the stimulatory effect of hyperglycaemia on DDR2 expression. Metformin also inhibited DDR2-dependent expression of Fibronectin and Collagen type I, indicating that it regulates these matrix proteins via DDR2 inhibition. The findings identify DDR2, a mediator of cardiovascular remodelling, as a molecular target of metformin, thereby uncovering the molecular basis of its protective role in vascular fibrosis and possibly cardiac fibrosis associated with diabetic cardiomyopathy.

Elevated ITGA2 expression promotes collagen type I-induced clonogenic growth of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) arises along the peripheral bile ducts and is often accompanied by a tumor microenvironment (TME) high in extracellular matrices (ECMs). In this study, we aimed to evaluate whether an ECM-rich TME favors iCCA progression. We identified ITGA2, which encodes collagen-binding integrin α2, to be differentially-expressed in iCCA tumors compared with adjacent normal tissues. Elevated ITGA2 is also positively-correlated with its ligand, collagen type I. Increased ITGA2 expression and its role in collagen type I binding was validated in vitro using four iCCA cell lines, compared with a non-cancerous, cholangiocyte cell line. Robust interaction of iCCA cells with collagen type I was abolished by either ITGA2 depletion or integrin α2β1-selective inhibitor treatment. In a phenotypic study, collagen type I significantly enhances clonogenic growth of HuCCA-1 and HuCCT-1 cells by three and sixfold, respectively. Inhibition of integrin α2 expression or its activity significantly blocks collagen type I-induced colony growth in both cell lines. Taken together, our data provide mechanistic evidence that collagen type I promotes growth of iCCA colonies through integrin α2 suggesting that the collagen type I—integrin α2 axis could be a promising target for cancer prevention and a therapeutic opportunity for this cancer.

The role of collagen type I/III ratio in the etiology of sacrococcygeal pilonidal.

The purpose of this study is to investigate whether there was a difference between the midline skin and the healthy skin in the lateral by means of total amount of collagen and Type I/III ratio which was the indicator of the collagen structure. Fifty patients with pilonidal sinus disease were enrolled. Samples were prepared from the midline skin of the sinus where the holes were located and lateral skin of the resected material. It was determined that the lateral line had significantly more collagen intensity and a higher collagen Type I/III ratio (p < 0.001). One of the reasons why hair mostly pricks into the midline in the intergluteal sulcus in pilonidal sinus disease is the fact that the amount of total collagen and collagen Type I/III ratio of the midline are lower than those of the lateral tissue. Complications are more common in cases with low Type I/III ratio and low total collagen rates.

Emodin induces collagen type I synthesis in Hs27 human dermal fibroblasts.

Fibrillar collagen and elastic fibers are the main components of the dermal extracellular matrix (ECM), which confers mechanical strength and resilience to the skin. In particular, type I collagen produced by fibroblasts is the most abundant collagen that determines the general strength of the ECM, thereby contributing to the prevesntion of the skin-aging process. Although the natural anthraquinone derivative emodin (1,3,8-trihydroxy-6-methylanthraquinone) exerts numerous beneficial effects, including antiviral, anticancer, anti-inflammatory and wound-healing effects in diverse cells, the effect of emodin on collagen expression or skin aging is not fully understood. The present study demonstrated that exposure to emodin increased type I collagen synthesis in a concentration- and time-dependent manner in Hs27 human dermal fibroblasts. Subsequent experiments showed that emodin strongly increased collagen type I levels without altering cell proliferation or cellular matrix metalloproteinase-1 (MMP-1) expression. Additionally, it was determined that increased phosphorylation of 5' AMP-activated protein kinase, following emodin treatment, was responsible for increased type I collagen synthesis. These findings clearly indicate that emodin plays an important role in collagen type I synthesis in dermal fibroblasts, thereby making it a potential drug candidate for treating skin aging and wrinkles.

The role of collagen type 5 in the dermal stem cell niche

The role of collagen type 5 in the dermal stem cell niche

Role of collagen type IV in the pathogenesis of increased prenasal thickness in Down syndrome fetuses: sonographic and immunohistological findings.

The present study aims to compare the presence and localization of collagen type IV in the prenasal tissue of fetuses with and without Down syndrome (DS). Products of conception were obtained from mid-gestation uterine evacuations of 14 DS fetuses and 15 unaffected controls. Microdissection of the prenasal area and an analysis of the prenasal tissue specimens were performed by a single pathologist, blinded to the karyotype results. Immunohistological presence and localization of type IV collagen were analyzed in the basement membrane (BM), blood vessels, and stroma of the tissues. There were no statistically significant differences in the presence and localization of antibodies for collagen IV in the blood vessels and stroma between the two groups. However, the presence and localization of type IV collagen in the BM of the prenasal skin were significantly higher in DS specimens compared to the control group (P=0.023). When combining both groups altogether, a significant correlation was found between the increased prenasal thickness (PT) and the high presence and location of collagen type IV, irrespective of the karyotype results (Spearman's correlation; R=0.459; P=0.012). Using the immunohistochemistry technique, we were able to confirm the overexpression of collagen type IV in the BM of the prenasal area. This may explain the sonographic finding of increased PT seen mainly in DS fetuses.

The Role of Collagen Type I on Hematopoietic and Mesenchymal Stem Cells Expansion and Differentiation

The three dimensional scaffold of the bone marrow (BM) niches is composed of various elements including extracellular matrix proteins and cell types, such as collagen type I (Col I) and stroma cells. Interaction of stem cells with their microenvironment is important for their regulation. In the marrow, Col I is mostly localized in the endosteal regions. The objective of this work was to investigate the role of Col I in the regulation of Hematopoietic Stem Cells (HSC) and Mesenchymal Stem Cells (MSC) growth. Col I was extracted from rat tail tendons and its purity confirmed. Human BM MSCs and umbilical cord blood (UCB) CD34+cells were used as Stem Cell sources. MSCs were cultured in medium with serum while CB CD34+cells were cultured without serum with cytokines. The impact of increasing concentrations of Col I (0-50 µg mL-1for coating) on the growth of Hematopoietic Progenitor Cells (HPC) and MSCs was investigated by cytometry, microscopy and clonogenic progenitor assays. Only a minority of CD34+cells expressed the Col I receptor α2β1prior to culture, while the opposite was observed when hematopoietic cells were placed in culture. Col I coated surfaces reduced the expansion of hematopoietic cells by 25% compared to control, while expansions of myeloid and MK progenitors were either unchanged or negatively affected by Col I, respectively. The differentiation of HPCs was also affected on Col I as demonstrated by differences in the frequencies of various cell lineages, such as CD34+cells, megakaryocytes (MK), erythrocytes and others. In contrast to HPCs, Col I surfaces increased MSCs proliferation but had little impact on osteoblasts derived from MSCs. Taken together, this study provides new insights into the regulatory activities of Col I on Stem Cells residing in the marrow.

The role of collagen type I α2 polymorphisms: intracranial aneurysms in Koreans

Background The COL1A2 is located on chromosome 7q22.1, and mutations in this gene have been associated with the development of IAs. In this study, we investigated whether the rs42524 and rs2621215 polymorphisms of the COL1A2 gene are associated with the development of cerebral aneurysms in the Korean population. Methods This was a hospital-based case control study conducted at Chonnam University Hospital, Gwangju, Korea. The study population consisted of 320 patients who had been treated for IA and 189 healthy hospital-based controls (angiographically negative for an IA). Two polymorphic loci were amplified by polymerase chain reaction, namely, rs42524 in exon 28 and rs2621215 in intron 46 of the COL1A2 gene, and analyzed by RFLP using HhaI or BfaI restriction enzymes, respectively. Results The genotype frequencies of rs42524 in cases were 88.0%, 11.4%, and 0.6% for the GG, GC, and CC genotypes, respectively, and in controls were 88.9%, 10.0%, and 1.1%, respectively. Similarly, the genotype frequencies of rs2621515 in cases were 88.0%, 10.1%, and 0.2% for the TT, TG, and GG genotypes, respectively, and among controls were 92.1%, 7.9%, and 0%, respectively. Conclusion The rs2621215 SNP in intron 46 of the COL1A2 gene was found to be marginally associated with an increased risk of IA development in the Korean population examined. In contrast, rs42524 showed no association with an increased risk of IA development.

Involvement of phospholipase D1 in collagen type I production of human dermal fibroblasts

In the current study, the involvement of phospholipase D (PLD) in the regulation of collagen type I production was examined using human dermal fibroblasts. Procollagen I production in the cells overexpressing PLD1, but not PLD2, was found to be increased compared with those in the vector control cells. To investigate the role of PLD1, we examined the effect of knockdown of endogenous PLD1 by small interference RNA (siRNA) on collagen production. The reduction of expression levels of PLD1 by siRNA transfection was accompanied by diminution of procollagen biosynthesis and also ribosomal S6 kinase 1 (S6K1) phosphorylation. The activity of mammalian target of rapamycin (mTOR) is essential for phosphorylation of S6K1 and the treatment of dermal fibroblasts with rapamycin, a potent inhibitor of mTOR abolished procollagen I production. These results suggest that PLD1 plays a crucial role in collagen type I production through mTOR signaling in human dermal fibroblast.

Effects of Transforming Growth Factor β1 on Bonelike Tissue Formation in Three-Dimensional Cell Culture. I. Culture Conditions and Tissue Formation

Bone tissue engineering based on growing bone marrow stromal cells on poly(L-lactic-co-glycolic acid) fiber meshes suffers from limited matrix production and mineralization when the cells are cultured with the standard differentiation supplements (dexamethasone, beta-glycerophosphate, and ascorbic acid). To overcome this problem we included transforming growth factor beta1 (TGF-beta1), which is described as playing a key role in collagen type I formation, although its effect on mineralization is controversially discussed. The investigations focused on establishing culture conditions for the application of TGF-beta1 in three-dimensional cell culture and on the effects of different doses of TGF-beta1 (1-20 ng/mL) on bonelike extracellular matrix formation. Immunohistochemical staining showed that TGF-beta1 enhanced the formation of procollagen type I, collagen type I, and collagen type V, especially under dynamic culture conditions (orbital shaker). A long-term study confirmed positive effects on the formation of extracellular matrix, which penetrated the scaffold to a depth of 250 to 300 microm. Mineralization, qualified by scanning electron microscopy in combination with energy-dispersive X-ray analysis and evaluated by determination of the Ca2+ content per scaffold, was up to 1.7-fold increased by TGF-beta1 compared with the control. In conclusion, the growth factor TGF-beta1 seems to be effective in improving extracellular bonelike matrix formation in vitro.

The presence of collagen types II and X in medial coronoid processes of 21 dogs

SummaryThe purpose of this study was to determine collagen type II and X immunohistochemical staining characteristics of naturally-occurring fragmented medial coronoid processes (FMCP) in order to help delineate potential pathophysiological events associated with FMCP.34 surgically excised FMCP from 21 client-owned dogs and 16 intact medial coronoid processes from 8 mongrel dogs were examined. The specimens were categorized by the dog's age: &lt;12 months, 12–18 months, 18–24 months, &gt;24 months.The excised FMCP and normal medial coronoid processes were sectioned and stained with haematoxylin and eosin, safranin-O fast green, and toluidine blue. Sections were subjectively evaluated for tissue morphology, cell and matrix content, and proteoglycan staining. Immunohistochemical staining was performed for collagen types II and X. Sections were then subjectively evaluated for the location and intensity of staining.FMCP tissue demonstrated a wide variety of histological and immunohistochemical characteristics compared to normal medial coronoid processes. Significantly (P = 0.016) more normal dogs stained positive for collagen type X than dogs with FMCP in the &lt;12 months old group. No other significant differences between affected and normal dogs were noted for either collagen type in any age group. No significant difference in age was noted for the presence or absence of collagen type II among affected dogs, and no statistically significant correlation was observed between age of those with collagens type X and type II present. Although not statistically significant (P = 0.100), there was a trend for the presence of collagen type II when collagen type X was present. The results of this study have not provided a definitive answer regarding the role of collagen type X in the etiopathogenesis of FMCP, but suggest that it may be an important factor in some cases, warranting further investigation. Excised fragmented medial coronoid processes were examined to determine the collagen immunohistochemical staining characteristics when compared to intact processes.

An immunohistochemical study examining the role of collagen type VI in the rodent periodontal ligament

The distribution of collagen types I and VI has been examined in the periodontal ligaments of rat incisor and molar teeth using cryosections and immunohistochemical staining procedures. The stain for collagen type I was uniform in all the ligaments examined. Uniform staining for collagen type VI was evident only in the ligament of the fully erupted molars, and the stain was absent from the mid-zone of the ligaments of the erupting molars and incisors. The staining pattern of the collagen type VI antibodies is consistent with previous reports which have suggested that the removal of collagen type VI precedes the degradation of major banded collagen fibrils in remodelling connective tissues. The removal of collagen type VI from the mid-zone of the incisor ligament may precede the remodelling events which facilitate tooth eruption.

Differential immunohistochemical localization of cytokeratins and collagen types I and III in experimentally‐induced cirrhosis

Liver cirrhosis was induced in male Wistar rats by subcutaneous injection (1 ml of 30 g/l) of an aqueous solution of thioacetamide. Using the indirect immunoperoxidase technique, high molecular weight keratins were localized in bile ducts and ductules. Low molecular weight cytokeratins were present in regenerating hepatocytes in active cirrhosis; bile ducts were unstained. These results suggest that cytokeratin staining may be useful in distinguishing bile duct epithelium and hepatocytes in hepatobiliary diseases. Anticollagen type III antibody stained hepatocytes and thin connective tissue fibres, while anticollagen type I antibody stained thicker fibres and some sinusoidal cells but not hepatocytes. Collagens were usually undetectable in normal liver cells. It is suggested, therefore, that hepatocytes may play a major role in collagen type III production which precedes the deposition of collagen type I. By contrast, collagen type I may be produced by fibroblasts and some cells along sinusoids (e.g. perisinusoidal fat-storing cells) after liver injury.