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Fibrosis


Scope of this initiative within the CMB:

The ubiquitous appearance of extracellular matrix during embryogenesis is integral to successful development of a complex body plan. Fibroblasts in developing tissues initially secrete an interstitial matrix of types I and III collagens as architectural support for the emergence of specialized epithelial units surrounded by laminins, type IV collagen, nidogen, and proteoglycans comprising basement membrane.

Interstitial collagens also increase with age, or idiosyncratically following inflammation or wounding. This process is called fibrogenesis and can appear at any site in the body. Wound repairs, like in skin, are usually self-limited and controlled in dermal tissues by homeostatic mechanisms that regulate scar formation. For unclear reasons, this regulation fails during episodes of persistent organ inflammation. The fibrogenesis that accrues in organ tissues perniciously disturbs morphogenic cues as well as the physiologic harmony between the organ structure and function. This latter form of fibrosis is progressive, pathologic, and often detrimental to the host.

The pathophysiology of the fibrotic response is complex and multifaceted. Contributing fibroblasts derived from epithelium through epithelial-mesenchymal transition and in some cases activate as myofibroblasts or morph into pericytes around blood vessels. Local fibrogenesis broadly involves the synthesis of new matrix driven by cytokines and elaborate signaling pathways. Additionally, there is a unique modulation of proteolysis and apoptosis as well as a myriad of other biochemical changes. This initiative in the Center for Matrix Biology is focused on the origin, development, and response of fibroblasts in tissue susceptible to fibrosis. Investigators in this initiative use a variety of molecular, transgenic, biochemical, and histochemical approaches to answer important questions in organs of interest.

  Members (16)

Borza, Dorin-Bogdan
Davidson, Jeffrey M.
Harris, Raymond C.
Hudson, Billy G.
Neilson, Eric G.
Pedchenko, Vadim
Penn, John S.
Pozzi, Ambra
Rousseau, Bernard
Santoro, Samuel A.
Stricklin, George P.
Voziyan, Paul
Weaver, Alissa M.


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