LMCD1, also known as LIM and cysteine rich domains 1, is a transcription factor with functions in protein-protein interactions and transcriptional co-repressor activity. It is involved in multiple signaling pathways, such as the calcineurin-NFAT signaling cascade, which is crucial for the recovery from acute kidney injury. LMCD1 is also important in processes like cell proliferation, metabolism, and epithelial-mesenchymal transition, and thus has significance in development, tissue repair, and disease [1,2].

In renal fibrosis, studies using a 7-day unilateral ureteral obstruction (7UUO) mouse model and adenovirus vectors carrying short hairpin RNA targeting LMCD1 showed that LMCD1 silencing ameliorated renal collagen deposition, reduced profibrotic factors, alleviated tubulointerstitial inflammation, and suppressed NLRP3 inflammasome activation and NFATc1 nuclear translocation. In a UUO model, knockdown of LMCD1 mitigated renal histopathological changes, decreased fibrotic gene expression, and blocked ERK signaling activation [3,4]. In testicular function, ablation of endogenous LMCD1 expression in Sertoli cells using an in vivo siRNA approach caused lipid accumulation, senescence, and impaired male fertility, as LMCD1 regulates phagocytosis by Sertoli cells through the NFAT1/Txlna signaling pathway [5].

In conclusion, LMCD1 is essential in various biological processes. Model-based research, especially using gene-knockdown mouse models, has revealed its roles in renal fibrosis and testicular function. Understanding LMCD1 can potentially provide new therapeutic targets for diseases related to these processes, such as chronic kidney disease and male infertility.

References:

1. Yalman, Nesil. . LMCD1 antisense RNA 1 is a newly identified long noncoding RNA. In Anti-cancer drugs, 33, 1-5. doi:10.1097/CAD.0000000000001124. https://pubmed.ncbi.nlm.nih.gov/34232945/

2. Ye, Zhikai, Chen, Ge, Hou, Cuicui, Wang, Erkang, Wang, Jin. 2022. LMCD1 facilitates the induction of pluripotency via cell proliferation, metabolism, and epithelial-mesenchymal transition. In Cell biology international, 46, 1409-1422. doi:10.1002/cbin.11858. https://pubmed.ncbi.nlm.nih.gov/35842772/

3. Bai, Yu, Tian, Mi, He, Ping, Lan, Jingsi, Zhang, Beiru. 2023. LMCD1 is involved in tubulointerstitial inflammation in the early phase of renal fibrosis by promoting NFATc1-mediated NLRP3 activation. In International immunopharmacology, 121, 110362. doi:10.1016/j.intimp.2023.110362. https://pubmed.ncbi.nlm.nih.gov/37311356/

4. Yu, Rui, Tian, Mi, He, Ping, Zhang, Yongzhe, Zhang, Beiru. 2021. Suppression of LMCD1 ameliorates renal fibrosis by blocking the activation of ERK pathway. In Biochimica et biophysica acta. Molecular cell research, 1869, 119200. doi:10.1016/j.bbamcr.2021.119200. https://pubmed.ncbi.nlm.nih.gov/34968577/

5. Jin, Xiaohang, Zhang, Sheng, Ding, Tianbing, Zhang, Yuxing, Li, Wei. 2020. Testicular Lmcd1 regulates phagocytosis by Sertoli cells through modulation of NFAT1/Txlna signaling pathway. In Aging cell, 19, e13217. doi:10.1111/acel.13217. https://pubmed.ncbi.nlm.nih.gov/32840323/