Upregulation of distinct collagen transcripts in post-surgery scar tissue: a study of conjunctival fibrosis

• Published in: Disease models & mechanisms Vol. 10; no. 6; pp. 751 - 760
• Main Authors: Seet, Li-Fong, Toh, Li Zhen, Chu, Stephanie W L, Finger, Sharon N, Chua, Jocelyn L L, Wong, Tina T
• Format: Journal Article
• Language: English
• Published: England The Company of Biologists Ltd 01-06-2017; The Company of Biologists
• Subjects: Animals; Cicatrix - etiology; Cicatrix - genetics; Collagen; Collagen - genetics; Collagen - metabolism; Conjunctiva; Conjunctiva - pathology; Connective tissue; Extracellular matrix; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Gene expression; Glaucoma; Humans; Localization; Mice; Ostomy; Proteins; RNA, Messenger - genetics; RNA, Messenger - metabolism; Scars; Surgery; Transcriptome - genetics; Transforming Growth Factor beta2 - pharmacology; Up-Regulation - drug effects; Wound healing; Wound Healing - drug effects; Conjunctiva; Collagen; Fibrosis
• ISSN: 1754-8403; 1754-8411
• DOI: 10.1242/dmm.028555

Excessive accumulation of collagen is often used to assess the development of fibrosis. This study aims to identify collagen genes that define fibrosis in the conjunctiva following glaucoma filtration surgery (GFS). Using the mouse model of GFS, we have identified collagen transcripts that were upregulated in the fibrotic phase of wound healing via RNA-seq. The collagen transcripts that were increased the most were encoded by
,
and
Further analysis of the
,
and
transcripts revealed their increase by 67-, 54- and 18-fold, respectively, in the fibrotic phase, compared with 12-fold for
, the most commonly evaluated collagen gene for fibrosis. However, only type I collagen was significantly upregulated at the protein level in the fibrotic phase. Type VIII and type I collagens colocalized in fibrous structures and in ACTA2-positive pericytes, and appeared to compensate for each other in expression levels. Type XI collagen showed low colocalization with both type VIII and type I collagens but can be found in association with macrophages. Furthermore, we show that both mouse and human conjunctival fibroblasts expressed elevated levels of the most highly expressed collagen genes in response to TGFβ2 treatment. Importantly, conjunctival tissues from individuals whose GF surgeries have failed due to scarring showed 3.60- and 2.78-fold increases in type VIII and I collagen transcripts, respectively, compared with those from individuals with no prior surgeries. These data demonstrate that distinct collagen transcripts are expressed at high levels in the conjunctiva after surgery and their unique expression profiles may imply differential influences on the fibrotic outcome.