Elsevier

Gene Expression Patterns

Volume 6, Issue 8, 2 October 2006, Pages 935-940
Gene Expression Patterns

Expression analysis of the novel gene collagen triple helix repeat containing-1 (Cthrc1)

https://doi.org/10.1016/j.modgep.2006.03.008Get rights and content

Abstract

We recently identified collagen triple helix repeat containing-1 (Cthrc1) as a novel gene induced in adventitial fibroblasts after arterial injury. Cthrc1 is a 30 kDa secreted protein that has the ability to inhibit collagen matrix synthesis. Cthrc1 is also glycosylated and retains a signal sequence consistent with the presence of Cthrc1 in the extracellular space. In injured arteries and skin wounds, we have found Cthrc1 expression to be associated with myofibroblasts and sites of collagen matrix deposition. Furthermore, we demonstrated that Cthrc1 inhibits collagen matrix deposition in vitro. Using in situ hybridization and immunohistochemistry, we characterized the expression domains of Cthrc1 during murine embryonic development and in postnatal tissues. In mouse embryos, Cthrc1 was expressed in the visceral endoderm, notochord, neural tube, developing kidney, and heart. Abundant expression of Cthrc1 was observed in the developing skeleton, i.e., in cartilage primordia, in growth plate cartilage with exclusion of the hypertrophic zone, in the bone matrix and periostium. Bones from adults showed expression of Cthrc1 only in the bone matrix and periostium while the articular cartilage lacked expression. Cthrc1 is typically expressed at epithelial–mesenchymal interfaces that include the epidermis and dermis, basal corneal epithelium, airway epithelium, esophagus epithelium, choroid plexus epithelium, and meninges. In the adult kidney, collecting ducts and distal tubuli expressed Cthrc1. Collectively, the sites of Cthrc1 expression overlap considerably with those reported for TGF-β family members and interstitial collagens. The present study provides useful information towards the understanding of potential Cthrc1 functions.

Section snippets

Expression of Cthrc1 mRNA during mouse embryonic development

Whole mount in situ hybridization was used to examine Cthrc1 mRNA expression during early mouse development. At 8.5 dpc Cthrc1 mRNA was prominently expressed in the notochord with a caudal to rostral gradient (Fig. 1A, nc). Expression was also seen in the floor plate of the anterior ventral neural tube (Fig. 1B, fp). Somitic expression became evident at 9.5 dpc (Fig. 1C, s) and prominent expression of Cthrc1 mRNA was also seen in the branchial arches (Fig. 1C, ba). Several regions in the head

Animals

All protocols using rodents were approved by the Institutional Animal Care and Use Committee and were in compliance with all federal and local guidelines. Mice were of the FVB and rats of the Sprague–Dawley strain.

Immunohistochemistry

Tissues were fixed in Methyl Carnoy’s fixative and embedded in paraffin. Sections of mouse bones were decalcified prior to embedding by incubation in 0.3 M EDTA solution for 14 days. Sections were treated with 1% 2-mercaptoethanol for 30 min prior to incubation with anti-CTHRC1

Acknowledgments

Funding for the studies was provided by NIH Grants HL69182 (V.L.) and P20 RR-15555 from the National Center for Research Resources. Histology services were supported by award P20 RR18789 from the National Center for Research Resources. Tahir Durmus is the recipient of a predoctoral fellowship from the Deutscher Akademischer Austauschdienst as part of the Biomedical Sciences Exchange Program.

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