Objective
Interstitial lung disease (ILD) is a serious complication and leading cause of mortality in patients with systemic sclerosis (SSc). In this study, we explored the role of LIM and cysteine‐rich domains protein 1 (LMCD1) as a novel factor in the pathogenesis of SSc‐related ILD (SSc‐ILD).
Methods
The expression and effects of LMCD1 were studied in lung tissue samples and fibroblasts from SSc‐ILD patients and control subjects as well as in lung tissue samples from animal models.
Results
LMCD1 was consistently elevated in lung tissue samples and in fibroblasts isolated from SSc‐ILD patients as compared to controls. Additionally, LMCD1 was found to be highly expressed in the lung in the fibroblast‐specific protein (FSP)–driven, constitutively active transforming growth factor β receptor type I (TGFβR1) transgenic mouse model of ILD and the bleomycin‐induced mouse model of ILD. In lung fibroblasts from SSc‐ILD patients, LMCD1 is an essential factor for the TGFβ‐induced generation of type I collagen, fibronectin, and α‐smooth muscle actin (α‐SMA). Depletion of LMCD1 by small interfering RNA reduced the expression of extracellular matrix proteins and lowered transcriptional activity and expression of α‐SMA, as well as decreased the proliferation and contractile activity of SSc‐ILD lung fibroblasts. In dense fibrotic areas of affected lung tissue, lung LMCD1 colocalized with α‐SMA. In cultured scleroderma lung fibroblasts, LMCD1 colocalized and interacted with serum response factor which mediates LMCD1‐induced contractile activity of lung fibroblasts.
Conclusion
Our study identifies LMCD1 as a profibrotic molecule contributing to the activation of myofibroblasts and the persistent fibroproliferation observed in SSc‐ILD. Thus, LMCD1 may be a potential novel therapeutic target for patients with SSc‐ILD.
This short review summarizes our laboratory’s development of benzylboronic esters as nucleophiles. Activation of the benzylboronic ester is achieved by irreversible coordination of an alkyllithium Lewis base to form a nucleophilic benzylboronate. This boronate was found to react with aldehydes, imines, ketones and alkyl bromides. A copper catalyst was employed in reactions of the boronate with epoxides and aziridines.
The mycobacteriophages InvictusManeo (K5 subcluster) and Netyap (L2 subcluster) were isolated from soils in Cullowhee Creek, Cullowhee, North Carolina. Both exhibit
Siphoviridae
morphology and infect
Mycobacterium smegmatis
mc
2
155. The InvictusManeo genome is 61,147 bp and contains 96 predicted protein-coding genes, whereas the Netyap genome is 76,366 bp with 131 predicted protein-coding genes.
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