TO THE EDITOR: We read with interest the recent article by Pan et al. (4) describing that Bcl-2 adenovirus E1B 19 kDainteracting protein 3 (Bnip3) may represent a potential target for the treatment of airway remodeling in asthma. Indeed, they clearly demonstrated that Bnip3 level was increased in airway smooth muscle (ASM) from asthmatic patients compared with that of healthy individuals. They also showed that Bnip3 was involved in asthmatic ASM cell proliferation, migration, and adhesion.

more »

... Bnip3 is an outer mitochondrial membrane adaptor that plays a role in mitochondrial turnover (8), Pan et al. (4) were able to decrease both mitochondrial density and cell number using siRNA against Bnip3 in ASM from asthmatic patients. Thus, this study supports the concept that mitochondria and mitochondria-associated proteins could be potential targets to decrease ASM mass in asthma. We fully agree with this concept since we previously reported the pivotal role of mitochondria in asthmatic ASM cell proliferation (6). Of note, in this study, Pan et al. (4) evaluated ASM cell proliferation using the CyQuant assay, which only reflects the number of cells. They demonstrated that siRNA against Bnip3 decreases ATP production and increases reactive oxygen species production. All these features may have been the consequence of an excess of ASM cell death (1), which was not evaluated in the present study. In a previous publication from the same group, Bnip3 silencing, although for a shorter duration of 24 h, had no effect on spontaneous cell death (3). In this connection, evaluation of cell cycles and/or bromodeoxyuridine incorporation would have strengthened the interpretation that ASM cell proliferation actually decreases upon Bnip3 silencing. Pan et al. (4) also evaluated ASM cell migration using wound healing assays. They showed that Bnip3 silencing reduces the recovery of the gap and thus suggested a decrease in cell migration. However, these experiments were performed from the 30th to the 72nd hour, a duration largely longer than that of the doubling time of asthmatic ASM cells, which is approximately 20 h (6). Thus, if ASM cell proliferation was effectively reduced or cell death increased upon Bnip3 silencing, an actual decrease in ASM cell migration remains to be demonstrated. To date, two pharmacological compounds (i.e., gallopamil and fevipiprant) have been shown to decrease ASM mass in vivo (2, 5) of which only gallopamil targets mitochondria (6). Moreover, the increased mitochondrial biogenesis, which we initially described (6), appears to be more complex since it also involves p53 (7) . Further studies on this issue obviously remain necessary. The study published by Pan et al. (4) is thus an important contribution toward identifying potential original targets. DISCLOSURES No conflicts of interest, financial or otherwise, are declared by the authors. AUTHOR CONTRIBUTIONS F.B. drafted manuscript; R.M. and P.B. edited and revised manuscript; F.B., R.M., and P.B. approved final version of manuscript. REFERENCES 1. Edinger AL, Thompson CB. Death by design: apoptosis, necrosis and autophagy. Selective dysfunction of p53 for mitochondrial biogenesis induces cellular proliferation in bronchial smooth muscle from asthmatic patients.