| First Author | Islam S | Year | 2022 |
| Journal | Matrix Biol | Volume | 107 |
| Pages | 59-76 | PubMed ID | 35176450 |
| Mgi Jnum | J:330258 | Mgi Id | MGI:6887275 |
| Doi | 10.1016/j.matbio.2022.02.004 | Citation | Islam S, et al. (2022) Accumulation of versican and lack of versikine ameliorate acute colitis. Matrix Biol |
| abstractText | Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan that plays a key role in the formation of the provisional matrix. Here, we generated dextran sulfate sodium-induced colitis in knockin-mice, R/R, expressing ADAMTS-resistant versican, and investigated the impact of accumulating versican and its turnover in the inflammatory colon mucosa. Histologically, R/R colon showed decreased levels of tissue destruction and an increased number of myofibroblasts and macrophages. Characterization of inflammatory cells revealed an increase in F4/80+ macrophages in R/R colon, compared with wild type, without a clear shift between M1 and M2 populations. Intestinal stroma exhibited a higher number of myofibroblasts in R/R, suggesting increased levels of tissue regeneration. Coculture of macrophages and stromal fibroblasts obtained from inflammatory colon showed that wild-type macrophages inhibited myofibroblastic differentiation of R/R fibroblasts but not wild-type. This inhibitory effect was due to an increased level of versikine, a cleaved fragment of versican by ADAMTS proteinases. Taken together, our results demonstrate versikine as the direct regulator that inhibits repair of inflamed tissue. |
