ADAM 28 is expressed by epithelial cells in human normal tissues and protects from C1q‐induced cell death

• Published in: The FEBS journal 2016-05, Vol.283 (9), p.1574-1594
• Main Authors: Miyamae, Yuka, Mochizuki, Satsuki, Shimoda, Masayuki, Ohara, Kentaro, Abe, Hitoshi, Yamashita, Shuji, Kazuno, Saiko, Ohtsuka, Takashi, Ochiai, Hiroki, Kitagawa, Yuko, Okada, Yasunori
• Format: Article
• Language: English
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/febs.13693

ADAM 28 (disintegrin and metalloproteinase 28), which was originally reported to be lymphocyte‐specific, is over‐expressed by carcinoma cells and plays a key role in cell proliferation and progression in human lung and breast carcinomas. We studied ADAM 28 expression in human normal tissues and examined its biological function. By using antibodies specific to ADAM 28, ADAM 28 was immunolocalized mainly to epithelial cells in several tissues, including epididymis, bronchus and stomach, whereas lymphocytes in lymph nodes and spleen were negligibly immunostained. RT ‐ PCR , immunoblotting and ELISA analyses confirmed the expression in these tissues, and low or negligible expression by lymphocytes was found in the lymph node and spleen. C1q was identified as a candidate ADAM 28‐binding protein from a human lung cDNA library by yeast two‐hybrid system, and specific binding was demonstrated by binding assays, immunoprecipitation and surface plasmon resonance. C1q treatment of normal bronchial epithelial BEAS ‐2B and NHBE cells, both of which showed low‐level expression of ADAM 28, caused apoptosis through activation of p38 and caspase‐3, and cell death with autophagy through accumulation of LC 3‐ II and autophagosomes, respectively. C1q‐induced cell death was attenuated by treatment of the cells with antibodies against the C1q receptor gC1qR/p33 or cC1qR/calreticulin. Treatment of C1q with recombinant ADAM 28 prior to addition to culture media reduced C1q‐induced cell death, and knockdown of ADAM 28 using si RNA s increased cell death. These data demonstrate that ADAM 28 is expressed by epithelial cells of several normal organs, and suggest that ADAM 28 plays a role in cell survival by suppression of C1q‐induced cytotoxicity in bronchial epithelial cells.