ALMS1-Deficient Fibroblasts Over-Express Extra-Cellular Matrix Components, Display Cell Cycle Delay and Are Resistant to Apoptosis
Figure 6
Model of fibrosis in Alström Syndrome.
Fibroblasts carrying ALMS1 mutations display an elongated shape, proliferate slowly, but are still responsive to pro-fibrotic factors and resistant to cell-death stimuli, suggesting that their proliferation is not controlled by apoptosis. ALMS1 mutated fibroblasts persist, continue to proliferate and to synthesize and secrete high levels of ECM, responsible for progressively remodeling and destroying normal tissue architecture, resulting in fibrosis. The microenvironment could be characterized by an excess of mediators enhancing a cellular pro-fibrotic phenotype, that together with inflammatory reactions could stimulate the fibrosis in an autocrine loop.