title: TGF-β1 promotes bovine mammary fibroblast proliferation through the ERK 1/2 signalling pathway.
abstract: The abnormal proliferation of bovine mammary fibroblasts (BMFBs) impairs mammary gland development and lactation. Severe manifestations develop into breast fibrosis, leading to the culling of cows and causing serious losses to the dairy industry. Transforming growth factor β1 (TGF-β1) is an important modulator of cell proliferation and extracellular matrix formation; however, limited information is available on BMFBs. In this study, a convenient and stable culture method for BMFBs was established. Treatment with 5 ng/mL of TGF-β1 significantly promoted the proliferation of BMFBs and accelerated the cell cycle. TGF-β1 stimulation for up to 12 h significantly increased the relative ERK1/2 mRNA expression and enhanced the protein expression of p-ERK1/2 and cyclin D1. Conversely, the ERK1/2 inhibitor PD98059 blocked these TGF-β1 effects. Further exploration using a mouse model showed that TGF-β1 significantly increased the proportion of fibroblasts and accelerating the cell transition from the G1 to G2/M phases. In addition, TGF-β1 enhanced the expression of fibrosis markers, α-SMA and I Collagen, which could be blocked efficiently by the PD98059 in mouse mammary gland. Finally, immunofluorescence analysis confirmed that TGF-β1 promoted fibroblast proliferation in healthy dairy cows after normal long-term dietary corn straw roughage supplementation. It is suggested that the diet may promote mammary fibroblast proliferation by raising the level of TGF-β1. Our study provides new insights into how nutrition causes undesirable changes in mammary gland structure.
authors.affiliation: College of Animal Science, Jilin University, Changchun, Jilin, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Animal Science, Jilin University, Changchun, Jilin, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Animal Science, Jilin University, Changchun, Jilin, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Xia
authors.affiliation: College of Animal Science, Jilin University, Changchun, Jilin, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, China.
authors.forename: Yanyi
authors.initials: Y
authors.lastname: Che
authors.affiliation: College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, Jilin University, Xi'an Road 5333, Changchun, Jilin, China.
authors.forename: Liancheng
authors.initials: L
authors.lastname: Lei
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000139:chemically induced / Q000473:pathology; D018929:Cell Culture Techniques / Q000379:methods / Q000662:veterinary*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000662:veterinary; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D053773:Transforming Growth Factor beta1 / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D053773:Transforming Growth Factor beta1; D019938:Cyclin D1
keywords: ERK 1/2 signalling pathway; TGF-β1; fibroblasts; proliferation