In the kidney, the α 8 integrin chain (itga8) is expressed in mesenchymal cells and is upregulated in fi brotic disease. We hypothesized that itga8 mediates a profi brotic phenotype of renal cells by promoting extracellular matrix and cytokine expression. Genetic itga8 defi ciency caused complex changes in matrix expression patterns in mesangial and smooth-muscle cells, with the only concordant effect in both cell types being a reduction of collagen III expression. Silencing of itga8 with siRNA led to a decline of matrix turnover with repression of matrix metalloproteinases and reduction of matrix production. In contrast, de novo expression of itga8 in tubular epithelial cells resulted in reduced collagen synthesis. Overexpression of itga8 in fi broblasts did not change the expression of matrix molecules or regulators of matrix turnover. Thus, the infl uence of itga8 on the expression of matrix components was not uniform and celltype dependent. Itga8 seems unlikely to exert overall profi brotic effects in renal cells.