title: MRP1 knockdown down-regulates the deposition of collagen and leads to a reduced hypertrophic scar fibrosis.
abstract: Multidrug resistance-associated protein 1 (MRP1) belongs to ATP-binding cassette transporters family. The overexpression of MRP1 is predominantly related with the failure of chemo-radiotherapy in various tumors. However, its possible role in hypertrophic scar (HS) is hardly investigated. Here we showed that the mRNA level and protein expression of MRP1 were higher in HS and HS derived fibroblasts (HSFs) than that in normal skin (NS) and NS derived fibroblasts (NSFs). Immunohistochemistry and immunofluorescence showed that the percentage of positive cells was higher in HS and HSFs. Meanwhile, the co-localization of MRP1 and α-SMA was stronger in HS. MRP1 knockdown in HSFs provoked a significant reduction in the protein expressions of collagen 3 and α-SMA in vitro. Moreover, MRP1 siRNA transfection could decrease the deposition of collagen in cultured tissues ex vivo and inhibit the scar formation in rabbit ear scar model in vivo. H&E staining and Masson trichrome staining revealed thinner and more orderly arranged collagen fiber in the MRP1 siRNA transfection group. The appearance of scar was improved as well. All these results indicate that MRP1 plays an important role in the formation of HS, MRP1 knockdown could be a potential method to reduce the accumulation of collagen and to improve the abnormal deposition of extracellular matrix in HS, which indicates that down-regulation of MRP1 has the potential therapeutic effect in the treatment and prophylaxis of HS.
authors.affiliation: Department of Burns and Cutaneous Surgery, Xijing Hospital, Fourth Military Medical University, 127 West Chang-le Road, Xi'an, 710032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Longlong
authors.initials: L
authors.lastname: Yang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zheng
authors.forename: Jihong
authors.initials: J
authors.lastname: Shi
authors.forename: Xue
authors.initials: X
authors.lastname: Wu
authors.forename: Hao
authors.initials: H
authors.lastname: Guan
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Jia
authors.forename: Ke
authors.initials: K
authors.lastname: Tao
authors.forename: Hongtao
authors.initials: H
authors.lastname: Wang
authors.forename: Shichao
authors.initials: S
authors.lastname: Han
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gao
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Linlin
authors.initials: L
authors.lastname: Su
authors.forename: Dahai
authors.initials: D
authors.lastname: Hu
mesh_terms: D000818:Animals; D002460:Cell Line; D017439:Cicatrix, Hypertrophic / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits
chemical_list: D003094:Collagen; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D034741:RNA, Small Interfering; C421109:multidrug resistance-associated protein 1