Matrix Metalloproteinases and Their Inhibitors in Turnover and Degradation of Extracellular Matrix - Extracellular Matrix Degradation - page 14

Fig. 1.2 TIMPs use distinct mechanisms to regulate ECM turnover in the normal and injured
lung. (a) TIMP3 directly inhibits matrix degradation by MMPs during lung development and
throughout life. In the absence of TIMP3, increased MMP activity leads to enhanced ECM
degradation, which results in impaired bronchiole branching morphogenesis, as well as enlarged
airspaces in the aged lung. (b) Following injury, TIMP3 regulates matrix deposition by
controlling the release and activation of profibrotic factors, such as TGF

,byMMPs.In
Timp3 / mice, fibrosis is enhanced in the heart and lung following injury due to increased
TGF

b

signaling

b