Degradation fibroblasts

One limitation of enzyme replacement therapy is the targeting of enzyme proteins to appropriate sites of substrate accumulation. Administration of a cholesterol esterase conjugated to albumin results in the degradation of pathologic cholesterol ester accumulations within the lysosomes of fibroblasts from a patient with cholesterol ester storage disease (246). 

Recently, the notion that the chronicity of inflammation may not actually drive the fibrogenic process has been widely appreciated (Tables 1, 2, and 3). Some propose that it is indeed the alteration of the mesenchymal cell phenotypes that disrupts the balance between collagen synthesis and degradation in the wound-healing process, highlighted by clinical evidence that shows unsuccessful treatment of fibrosis with anti-inflammatory or immunosuppressive drugs (18,19). One scenario is that mesenchymal cells (myofibroblasts and fibroblasts) are phenotypically altered and thus do not undergo apoptosis after resolution. 

Inhibition of IFN-y entails inhibition of fibroblast proliferation and differentiation, subsequent collagen synthesis, and increased expression of MMP-1 to promote degradation of matrix (105). IFN-y also triggers robust T-lymphocyte... 

Z. Shahrokh, G. Eberlein, D. Buckley, M. V. Paranandi, D. W. Aswad, P. Stratton, R. Mischak, Y. J. Wang, Major Degradation Products of Basic Fibroblast Growth Factor Detection of Succinimide and iso-Aspartate in Place of Aspartate15 , Pharm. Res. 1994, 11, 936-944. 

The role of phosphorylation and degradation of hPER protein oscillation in normal human fibroblasts... 

To compare the molecular mechanisms of circadian clocks in divergent species, we cloned and analysed circadian mRNA expression of human clock genes in serum shocked fibroblasts. We also developed novel antisera and examined the temporal expression of three PER proteins (hPERl, hPER2, and hPER3). The results showed robust circadian profiles of hPER protein abundance, phosphorylation and degradation. 

FIG. 5. Role of phosphorylation and degradation of clock protein PER in human normal fibroblasts. After the phosphorylation of hPERl by casein kinase, the ubiquitin-proteosome pathway may be involved in its degradation in human cells. 

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