TY - JOUR
T1 - Mindin (SPON2) Is Essential for Cutaneous Fibrogenesis in a Mouse Model of Systemic Sclerosis
AU - Rana, Isha
AU - Kataria, Sunny
AU - Tan, Tuan Lin
AU - Hajam, Edries Yousaf
AU - Kashyap, Deepak Kumar
AU - Saha, Dyuti
AU - Ajnabi, Johan
AU - Paul, Sayan
AU - Jayappa, Shashank
AU - Ananthan, Akhil S.H.P.
AU - Kumar, Pankaj
AU - Zaarour, Rania F.
AU - Haarshaadri, J.
AU - Kansagara, Gaurav
AU - Rizvi, Abrar
AU - Zirmire, Ravindra K.
AU - Badarinath, Krithika
AU - Khedkar, Sneha Uday
AU - Chandra, Yogesh
AU - Samuel, Rekha
AU - George, Renu
AU - Danda, Debashish
AU - Jacob, Paul Mazhuvanchary
AU - Dey, Rakesh
AU - Dhandapany, Perundurai S.
AU - He, You Wen
AU - Varga, John
AU - Varghese, Shyni
AU - Jamora, Colin
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2023/5
Y1 - 2023/5
N2 - Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal models that recapitulate certain aspects of the human pathology. We found that the transcription factor SNAI1 is overexpressed in the epidermis of patients with systemic sclerosis, and a transgenic mouse recapitulating this expression pattern is sufficient to induce many clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin (SPON2) in fibrogenesis. Mindin is produced by SNAI1 transgenic skin keratinocytes and aids fibrogenesis by inducing early inflammatory cytokine production and collagen secretion in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.
AB - Systemic sclerosis is a fibrotic disease that initiates in the skin and progresses to internal organs, leading to a poor prognosis. Unraveling the etiology of a chronic, multifactorial disease such as systemic sclerosis has been aided by various animal models that recapitulate certain aspects of the human pathology. We found that the transcription factor SNAI1 is overexpressed in the epidermis of patients with systemic sclerosis, and a transgenic mouse recapitulating this expression pattern is sufficient to induce many clinical features of the human disease. Using this mouse model as a discovery platform, we have uncovered a critical role for the matricellular protein Mindin (SPON2) in fibrogenesis. Mindin is produced by SNAI1 transgenic skin keratinocytes and aids fibrogenesis by inducing early inflammatory cytokine production and collagen secretion in resident dermal fibroblasts. Given the dispensability of Mindin in normal tissue physiology, targeting this protein holds promise as an effective therapy for fibrosis.
UR - http://www.scopus.com/inward/record.url?scp=85147371481&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85147371481&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2022.10.011
DO - 10.1016/j.jid.2022.10.011
M3 - Article
C2 - 36528128
AN - SCOPUS:85147371481
SN - 0022-202X
VL - 143
SP - 699-710.e10
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 5
ER -