Upregulation of gamma-2 laminin-332 in the mouse ear vesicant wound model.
Epithelial cell migration during wound healing is regulated in part by enzymatic processing of laminin-332 (formerly LN-5), a heterodimer formed from alpha, beta, and gamma polypeptide chains. Under static conditions, laminin-332 is secreted into the extracellular matrix as a proform and has two chains processed to smaller forms, allowing it to anchor epithelial cells to the basement membrane of the dermis. During incisional wounding, laminin gamma2 chains in particular are processed to smaller sizes and function to promote epithelial sheet migration over the wound bed. The present study examines whether this same function occurs following chemical injury. The mouse ear vesicant model (MEVM) was used to follow the pathology in the ear and test whether processed laminin-332 enhances epithelial cell migration. Skin biopsies of sulfur mustard (SM) exposed ears for several time points were analyzed by histology, immunohistochemistry, real-time PCR, and Western blot analysis. SM exposure greatly increased mRNA levels for laminin-gamma2 in comparison to the other two chains. Protein production of laminin-gamma2 was upregulated, and there was an increase in the processed forms. Protein production was in excess of the amount required to form heterotrimeric laminin-332 and was associated with the migrating epithelial sheet, suggesting a potential role in wound healing for monomeric laminin-gamma2.
Chang
Yoke-Chen
YC
Department of Pharmacology & Toxicology, Ernest Mario School of Pharmacy, Rutgers University, EOHSI, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Sabourin
Carol L K
CL
Lu
Shou-En
SE
Sasaki
Takako
T
Svoboda
Kathy K H
KK
Gordon
Marion K
MK
Riley
David J
DJ
Casillas
Robert P
RP
Gerecke
Donald R
DR
D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000378:metabolism; D002465:Cell Movement; D004195:Disease Models, Animal; D004423:Ear / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007797:Laminin / Q000096:biosynthesis* / Q000378:metabolism; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation; D014945:Wound Healing; D014947:Wounds and Injuries / Q000378:metabolism* / Q000473:pathology; D000097794:Kalinin
D015815:Cell Adhesion Molecules; D007797:Laminin; D012333:RNA, Messenger; D000097794:Kalinin; C498522:Lamc2 protein, mouse