Abstract
Autophagy is a tightly regulated physiological process essential for cellular maintenance, differentiation, development, and homeostasis. Aberration of this process associates with the pathogeneses of several diseases in mammals. Hypertrophic scar (HS) is characterized by an abundance of collagenous tissue with hypercellularity. However, the molecular mechanism in HS formation is poorly understood. We compared the autophagic capacity in HS and its normal skin (NS) counterparts and explored the molecular mechanism of autophagy during the formation of HS. Microtubule-associated protein 1 light chain 3 (LC3) proteins in HS and NS were detected by immunohistochemistry, Western blot and quantitative real-time PCR (qPCR). The data showed that LC3 positive staining in HS was less intensive relative to NS group (p < 0.05). Three forms of LC3, with molecular weights of about 19 kDa (proLC3), 18 kDa (LC3-I) and 16 kDa (LC3-II), respectively, expressed in NS by Western blot. In contrast, only proLC3 expressed while both LC3-I and LC3-II were significantly downregulated in HS. The protein level of beclin 1 in HS was significantly lower compared with NS (p < 0.05). LC3 and beclin 1 mRNA levels in HS were significantly lower than that in NS (p < 0.05). These results suggest that the generation of LC3-I and LC3-II are interrupted in HS, and that the resultant decrease of autophagic capacity may associate with the pathogenesis of HS.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Asanuma K, Tanida I, Shirato I, Ueno T, Takahara H, Nishitani T, Kominami E, Tomino Y (2003) MAP-LC3 a promising autophagosomal marker, is processed during the differentiation and recovery of podocytes from PAN nephrosis. FASEB J 17:1165–1167
Jin S, White E (2008) Tumor suppression by autophagy through the management of metabolic stress. Autophagy 4:563–566
Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T (2000) LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 19:5720–5728
Kroemer G, Jaattela M (2005) Lysosome and autophagy in cell death control. Nat Rev Cancer 5:886–897
Levine B, Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132:27–42
Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T (2009) Two Beclin1-binding proteins, Atg14L and rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol 11:385–396
Meijer AJ, Dubbelhuis PF (2004) Amino acid signaling and the integration of metabolism. Biochem Biophys Res Commun 313:397–403
Mizushima N, Yoshimori T, Ohsumi Y (2003) Role of the Apg12 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 35:553–561
Niessen FB, Spauwen PH, Schalkwijk J, Kon M (1999) On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg 104:1435–1458
Ong CT, Khoo YT, Mukhopadhyay A, Do DV, Lim IJ, Aalami O, Phan TT (2007) mTOR as a potential therapeutic target for treatment of keloids and excessive scars. Exp Dermatol 16:394–404
Orvadahl A, Levine B (2009) Eating the enemy within: autophagy in infectious diseases. Cell Death Differ 16:57–69
Riddle DL, Gorski SM (2003) Shaping and stretching life by autophagy. Dev Cell 5:364–365
Shibata M, Yoshimura K, Furuya N, Koike M, Ueno T, Komatsu M, Arai H, Tanaka K, Kominami E, Uchiyama Y (2009) The MAP1-LC3 conjugation system is involved in lipid droplet formatiom. Biochem Biophys Res Commun 382:419–423
Shintani T, Kllonsky DJ (2004) Autophagy in heath and disease: a double-edged sword. Science 306:990–995
Tanida I, Minematsu-Ikequchi N, Ueno T, Kominami E (2005) Lysosomal turnover, but not a cellular level, of endogenous LC3 is a marker for autophagy. Autophagy 1:84–91
Tanida I, Ueno T, Kominami E (2004) LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 36:2503–2518
Todde V, Veenhuis M, van der Klei IJ (2009) Autophagy: principles and significance in health and disease. Biochim Biophy Acta 1792:3–13
Tanida I, Nishitani T, Nemoto T, Ueno T, Kominami E (2002) Mammalian Apg12p, but not the Apg12p-Apg5p conjugate, facilitates LC3 processing. Biochem Biophys Res Commun 296:1164–1170
van der Veer WM, Bloemen MC, Ulrich MM, Molema G, van Zuijen PP, Middelkoop E, Niessen FB (2009) Potential cellular and molecular causes of hypertrophic scar. Burns 35:15–29
Winslow AR, Rubinsztein DC (2008) Autophagy in neurodegeneration and development. Biochim Biophys Acta 1782:723–729
Wolfram D, Tzankov A, Pülzl P, Piza-Katzer H (2009) Hypertrophic scars and keloids-a review of their pathophysiology, risk factors, and therapeutic management. Dermatol Surg 35:171–181
Yen WL, Klionsky DJ (2008) How to live long and prosper: autophagy, mitochondria, and aging. Physiology 23:248–262
Yoshimori T (2004) Autophagy: a regulated bulk degradation process inside cells. Biochem Biophys Res Commun 313:453–458
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 30772249).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shi, JH., Hu, DH., Zhang, ZF. et al. Reduced expression of microtubule-associated protein 1 light chain 3 in hypertrophic scars. Arch Dermatol Res 304, 209–215 (2012). https://doi.org/10.1007/s00403-012-1204-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-012-1204-x