Compositions and methods for facilitating tissue repair by enhancing the actions of BIGH3 or at least one of its downstream effector molecules in injured tissue, and for the diagnosis, prophylactic and therapeutic treatment of fibrosis by inhibiting the actions of BIGH3 or at least one of its downstream effector molecules, such as PU.1 transcription factor and MMP14. Other disclosed methods include methods of screening and/or identifying compounds useful for facilitating tissue repair, treating fibrosis, or for altering the accumulation or deposition of collagen, comprising contacting BIGH3 or its downstream effector molecules, such as PU.1 or MMP14, with a substance and subsequently determining the effects of the substance on the activity of BIGH3, PU.1, or MMP14.