1393 Human TMEM2 is not a hyaluronidase but a regulator of hyaluronan metabolism

Hyaluronan (HA) is a high molecular weight linear glycosaminoglycan and abundant in the skin extracellular matrix. Cutaneous HA first depolymerized to intermediate sizes then further fragmented regional lymph nodes. High anti-inflammatory anti-angiogenic, whereas pro-inflammatory pro-angiogenic. We have reported that HYBID (HA-Binding protein Involved Depolymerization), also known as KIAA1199/CEMIP, responsible for step of depolymerization, but it was recently shown mouse TMEM2 (mTMEM2) with structural similarity HYBID, membrane-bound hyaluronidase. previously showed essential depolymerization normal human dermal fibroblasts (NHDF), knockdown (hTMEM2) enhanced depolymerization. The purpose this study elucidate degradation activity functions hTMEM2. expression plasmids were transfected into HEK293T cells, each confirmed. hHYBID mTMEM2 degraded HA, hTMEM2 did not, indicating does not function Then, we focused on amino acid residues are conserved HA-degrading hHYBID, mHYBID, substituted Simultaneous replacement corresponding (H248N A303F) GG domain abolished activity. In addition, stimulation NHDF by IL-1β increased mRNA subsequently decreased along an increase HAS2-dependent production, which reversed knockdown. Taken together, these results indicate hyaluronidase regulator metabolism.