Collagen gel induces apoptosis of epithelial cells: role of tensegrity

Ming-Jer Tang and Wen-Tai Chiu

Department of Physiology

National Cheng Kung University Medical College, Tainan, Taiwan.


  Previous studies in our laboratory showed that epithelial cells developed apoptosis when overlaid with type I collagen gel. However, whether epithelial cells develop apoptosis upon fibril collagen is not known. In this study, we established that collagen gel induced apoptosis of epithelial (NMuMG, BS-C-1, LLC-PK1, NRK-52E and MDCK) but not mesenchymal (293 and NIH-3T3) or tumor (HK-2, U-373 MG, and Chang Liver) cell lines. Among various extracellular matrix examined, only type III collagen exhibited similar effects, suggesting that collagen gel-induced apoptosis is a result specific to fibril collagen. Morphologically, these epithelial cells grown on collagen gel exhibited a more contracted cell type, lost microvilli and actively pulled collagen fibers. In addition, cell cultured on collagen gel exhibited markedly reduced cell as well as nuclear size. To delineate whether this contracted morphology is associated with apoptosis, we cultured cells on a thin layer of collagen gel or collagen prepared from rats of various ages. Collagen gel coating markedly decreased collagen gel-induced contracted morphology and attenuated collagen gel-induced apoptosis, but did not prevent the loss of microvilli. In addition, collagen gel prepared from older rat also reduced contracted morphology and apoptosis, possibly due to the reason that higher levels of cross-links in older collagen may stabilize or consolidate the hydrated gel structures. These results indicate that collagen fiber induces dedifferentiation and apoptosis of epithelial cells. Because collagen fiber is the major component of tubulointerstitial fibrosis, whether this may play a very important role in progressive renal failure is to be determined.