Upregulation of distinct collagen transcripts in post-surgery scar tissue: a study of conjunctival fibrosis.
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 byCol8a1,Col11a1andCol8a2Further analysis of theCol8a1,Col11a1andCol8a2transcripts revealed their increase by 67-, 54- and 18-fold, respectively, in the fibrotic phase, compared with 12-fold forCol1a1, 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.
Ocular Therapeutics and Drug Delivery, Singapore Eye Research Institute, 20 College Road, Singapore 169856 seet.li.fong@seri.com.sg tina.wong.t.l@singhealth.com.sg.|Duke-NUS Medical School, 8 College Road, Singapore 169857.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Rd, National University Hospital, Singapore 119074.
Li-Fong
0000-0003-0845-5918
LF
Seet
Ocular Therapeutics and Drug Delivery, Singapore Eye Research Institute, 20 College Road, Singapore 169856.
Li Zhen
LZ
Toh
Ocular Therapeutics and Drug Delivery, Singapore Eye Research Institute, 20 College Road, Singapore 169856.
Stephanie W L
SWL
Chu
Ocular Therapeutics and Drug Delivery, Singapore Eye Research Institute, 20 College Road, Singapore 169856.
Sharon N
SN
Finger
Glaucoma Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751.
Jocelyn L L
JLL
Chua
Ocular Therapeutics and Drug Delivery, Singapore Eye Research Institute, 20 College Road, Singapore 169856 seet.li.fong@seri.com.sg tina.wong.t.l@singhealth.com.sg.|Duke-NUS Medical School, 8 College Road, Singapore 169857.|Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Lower Kent Ridge Rd, National University Hospital, Singapore 119074.|Glaucoma Service, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751.|School of Materials Science and Engineering, Nanyang Technological University, 11 Faculty Ave, Singapore 639977.
Tina T
TT
Wong
D000818:Animals; D002921:Cicatrix / Q000209:etiology* / Q000235:genetics*; D003094:Collagen / Q000235:genetics* / Q000378:metabolism; D003228:Conjunctiva / Q000473:pathology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006801:Humans; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D053781:Transforming Growth Factor beta2 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
D012333:RNA, Messenger; D053781:Transforming Growth Factor beta2; D003094:Collagen
Collagen; Conjunctiva; Fibrosis